ClinVar Genomic Variation As It Relates To Human Health - NCBI
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Following Follow ⚠ Print Download Cite this record Close National Center for Biotechnology Information. ClinVar; [VCV000003038.104], https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000003038.104 (accessed Dec. 24, 2025). Copy Germline Reviewed by expert panel Help
HGVS
... more HGVS ... less HGVS Protein change - Other names IVS8-6T>G IVS10AS, T-G, -6 Canonical SPDI NC_000011.10:108248926:T:G Global minor allele frequency (GMAF) Help
Comment: The ATM c.1066-6T>G variant has a GnomAD (v2.1.1) filtering allele frequency of 0.2081% (NFE) which is above the ATM BS1 threshold of .05% (BS1). In silico predictors (SpliceAI Acceptor Loss 0.62; MaxEntScan -2.49) are indeterminate about whether this variant affects splicing. This variant has been observed in a homozygous and compound heterozygous state (presumed) in multiple individuals without Ataxia-Telangiectasia (BP2_Strong, GTR Lab IDs: 61756, 26957, 500031). In summary, this variant meets criteria to be classified as benign based on the ACMG/AMP criteria applied as specified by the HBOP Variant Curation Expert Panel OK Comment: Variant summary: ATM c.1066-6T>G alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. Although the variant was reported to be associated with a partial splicing defect (see e.g. Broeks_2000, Dork_2001, Fang_2010), several patient samples were also reported to have second-site mutations that could also affect splicing, therefor the splicing effect of the variant in isolation is currently unclear (Tavtigian_2009, Fievet_2019). The variant allele was found at a frequency of 0.0014 in 270694 control chromosomes, predominantly within the Non-Finnish European subpopulation at a frequency of 0.0024 in the gnomAD database (including 2 homozygotes). The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 2.4 fold of the estimated maximal expected allele frequency for a pathogenic variant in ATM causing Breast Cancer phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. In addition, the variant was reported to be found in the FLOSSIES database in 33/7325 European American women, who were older than age 70 years and have never had cancer. The allele frequency in this cohort is also higher than expected for a pathogenic variant in ATM causing Breast Cancer (0.0023 vs. 0.001), further supporting a benign role for the variant. Though the variant has been reported in the literature in homozygous individuals affected with Ataxia Telangiectasia (A-T), these patients carried second-site mutations that were sufficient to explain the A-T phenotype (Tavtigian_2009, Fievet_2019). The variant was also reported in compound heterozygosity, with (potential) pathogenic ATM variants in trans, in an individual affected with breast cancer (Fang_2010) and also in a patient with multiple myeloma and (per authors) an atypical, milder A-T phenotype (Austen_2008). Therefore these reports do not support the association of the variant with A-T. The variant, c.1066-6T>G, also has been reported in the literature in individuals affected with Breast Cancer, however in most of the cases co-occurrence and/or co-segregation data was not provided, therefore these reports do not provide unequivocal conclusions about association of the variant with Breast Cancer. Moreover, in case-control studies the variant did not have significantly increased risk association with breast cancer (Dork_2001, Bernstein_2006, Ding_2011). One recent case-control study reported the variant with an increased risk for CLL (OR: 3.29), however this analysis had a relatively small sample size and most patients were sporadic cases, thus this risk association might not be reliable (Tiao 2017). Twelve other submitters have provided clinical-significance assessments for this variant in ClinVar after 2014 (without evidence for independent evaluation), and classified the variant as VUS (4x), likely benign (3x) / benign (5x). Based on the evidence outlined above, the variant was classified as benign. OK Comment: ATM: PP3, BS2 OK Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. OK Comment: This variant is associated with the following publications: (PMID: 26898890, 28779002, 28643015, 21933854, 10677309, 15101044, 11606401, 25040471, 27067391, 26250988, 18573109, 26662178, 27798748, 27296296, 19781682, 16958054, 27803004, 28627265, 28691344, 16914028, 28652578, 20544271, 30549301, 11830610, 32918381) OK Comment: This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. OK Comment: BS1, BP2_mod OK Comment: This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. OK Comment: The ATM c.1066-6T>G variant was identified in 51 of 18,694 proband chromosomes (frequency: 0.003) from individuals or families with chronic lymphocatic leukemia, breast or ovarian cancer and was present in 70 of 27,754 control chromosomes (frequency: 0.003) from healthy individuals (Ding 2010, Tiao 2017). The variant was identified in dbSNP (rs201686625) as “with other allele”, ClinVar (classified as uncertain significance by Ambry Genetics, Integrated Genetics and 5 other submitters; as benign by Invitae, Color, Athena Diagnostics and 2 other submitters; and as likely benign by GeneDx and 2 other submitters) and LOVD 3.0 (observed 8x). The variant was identified in control databases in 357 of 266,346 chromosomes (2 homozygous) at a frequency of 0.001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 7 of 23,658 chromosomes (freq: 0.0003), Other in 2 of 6198 chromosomes (freq: 0.0003), Latino in 19 of 32,652 chromosomes (freq: 0.0006), European in 286 of 123,010 chromosomes (freq: 0.002), Finnish in 18 of 25,254 chromosomes (freq: 0.0007), and South Asian in 25 of 27,738 chromosomes (freq: 0.0009); it was not observed in the Ashkenazi Jewish or East Asian populations. The variant was identified by our laboratory in multiple patients with pathogenic variants in BRCA2 (including c.1929del, p.Arg645Glufs*15 and c.755_758del, p.Asp252Valfs*24). The variant was also identified in the homozygous state in a patient with ataxia telangiectasia (Dork 2001), for whom alternate pathogenic variants were subsequently identified (Tavtigian 2009). A patient with mild ataxia telangiectasia was found to carry this variant in the compound heterozygous state and had reduced ATM protein expression and kinase activity, indicating this variant does not fully abolish protein expression and function (Austen 2016). Additionally, this variant leads to an increase in exon 11 skipping, although some exon 11 skipping is found in controls who do not carry this variant (Soukupova 2007). The c.1066-6T>G variant is located in the 3' splice region and does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence; variants involving these positions sometimes affect splicing and 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. OK
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NM_000051.4(ATM):c.1066-6T>G
Cite Following Follow ⚠ Print Download Cite this record Close National Center for Biotechnology Information. ClinVar; [VCV000003038.104], https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000003038.104 (accessed Dec. 24, 2025). Copy Germline Reviewed by expert panel Help Reviewed by expert panel. Learn more about how ClinVar calculates review status.
Benign for ATM-related cancer predisposition Classification is based on the expert panel submission Mar 2022 by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Va… HelpThe classification is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
FDA Recognized Database SomaticNo data submitted for somatic clinical impact
SomaticNo data submitted for oncogenicity
Functional data are available for this variant
Variant Details
IdentifiersNM_000051.4(ATM):c.1066-6T>G
Variation ID: 3038 Accession: VCV000003038.104
Type and lengthsingle nucleotide variant, 1 bp
LocationCytogenetic: 11q22.3 11: 108248927 (GRCh38) [ NCBI UCSC ] 11: 108119654 (GRCh37) [ NCBI UCSC ]
Timeline in ClinVar| First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification. | Last submission Help The date of the most recent submission for each type of classification for this variant. | Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification. | |
|---|---|---|---|
| Germline | Sep 18, 2016 | Dec 14, 2025 | Mar 9, 2022 |
| Nucleotide | Protein | Molecularconsequence |
|---|---|---|
| NM_000051.4:c.1066-6T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration. | intron variant | |
| NM_001351834.2:c.1066-6T>G | intron variant | |
| NC_000011.10:g.108248927T>G | ||
| NC_000011.9:g.108119654T>G | ||
| NG_009830.1:g.31096T>G | ||
| LRG_135:g.31096T>G | ||
| LRG_135t1:c.1066-6T>G |
The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
0.00040 (G)
Allele frequency HelpThe frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00062
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00177
The Genome Aggregation Database (gnomAD) 0.00128
Exome Aggregation Consortium (ExAC) 0.00130
1000 Genomes Project 0.00040
The Genome Aggregation Database (gnomAD) 0.00139
Trans-Omics for Precision Medicine (TOPMed) 0.00156
Links ClinGen: CA151456 OMIM: 607585.0021 dbSNP: rs201686625 VarSome Comment on variantNCBI staff reviewed the sequence information reported in PubMed 12673794 to determine the location of IVS10–6T>G in the current reference sequence.
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases. | Related variants | ||
|---|---|---|---|---|---|---|
| HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. | TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. | Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. | All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. | |||
| ATM | Sufficient evidence for dosage pathogenicity | No evidence available | GRCh38GRCh37 | 11746 | 18957 | |
Conditions - Germline
| Condition Help The condition for this variant-condition (RCV) record in ClinVar. | Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) | Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. | Last evaluated Help The most recent date that a submitter evaluated this variant for the condition. | Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Ataxia-telangiectasia syndrome | Conflicting classifications of pathogenicity (5) | criteria provided, conflicting classifications | Feb 4, 2025 | RCV000003178.49 |
| Hereditary cancer-predisposing syndrome | Benign/Likely benign (5) | criteria provided, multiple submitters, no conflicts | Dec 10, 2020 | RCV000115132.21 |
| not specified | Benign (4) | criteria provided, multiple submitters, no conflicts | Mar 4, 2025 | RCV000200968.32 |
| not provided | Conflicting classifications of pathogenicity (10) | criteria provided, conflicting classifications | Oct 1, 2025 | RCV000488246.64 |
| Familial cancer of breast | Conflicting classifications of pathogenicity (2) | criteria provided, conflicting classifications | Jan 16, 2025 | RCV001253153.17 |
| Malignant tumor of breast | Likely benign (1) | no assertion criteria provided | - | RCV001355481.10 |
| Breast and/or ovarian cancer | Likely benign (1) | criteria provided, single submitter | Jun 23, 2023 | RCV001797991.12 |
| Ataxia-telangiectasia syndrome Familial cancer of breast | Likely benign (1) | criteria provided, single submitter | Nov 5, 2021 | RCV002496240.8 |
| ATM-related cancer predisposition | Benign (1) | reviewed by expert panel | Mar 9, 2022 | RCV005638395.1 |
| Intellectual disability | Uncertain significance (1) | criteria provided, single submitter | Dec 30, 2019 | RCV005624666.1 |
Submissions - Germline
| Classification Help The submitted germline classification for each SCV record. (Last evaluated) | Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) | Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. | Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. | Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|---|---|---|---|---|
| Benign (Mar 09, 2022) C Contributing to aggregate classification | reviewed by expert panel (clingen hbop acmg specifications atm v1-1) | ATM-related cancer predisposition (Autosomal dominant inheritance) | ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen FDA Recognized Database Accession: SCV002499287.2 First in ClinVar: Apr 16, 2022 Last updated: Sep 22, 2025 | Other databases https://erepo.clinicalgenome.org… https://erepo.clinicalgenome.org/evrepo/ui/interpretation/bccd9f16-4086-4c14-8d78-04c52ad58630 Comment: show The ATM c.1066-6T>G variant has a GnomAD (v2.1.1) filtering allele frequency of 0.2081% (NFE) which is above the ATM BS1 threshold of .05% (BS1). In silico predictors (SpliceAI Acceptor Loss 0.62; MaxEntScan -2.49) are indeterminate about whether this variant affects splicing. This variant has been observed in a homozygous and compound heterozygous state (presumed) in multiple individuals without Ataxia-Telangiectasia (BP2_Strong, GTR Lab IDs: 61756, 26957, 500031). In summary, this variant meets criteria to be classified as benign based on the ACMG/AMP criteria applied as specified by the HBOP Variant Curation Expert Panel (less) Observation: 1 Collection method: curation Allele origin: germline Affected status: unknown Observation 1 Collection method: curation Allele origin: germline Affected status: unknown |
| Benign (Jun 07, 2019) N Not contributing to aggregate classification | criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) | not specified | Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000694169.2 First in ClinVar: May 08, 2017 Last updated: Nov 10, 2019 | Publications: PubMed (25) PubMed: 20927582‚ 21933854‚ 15101044‚ 11606401‚ 18573109‚ 17393301‚ 19781682‚ 16958054‚ 14643952‚ 12673794‚ 10677309‚ 11830610‚ 20678261‚ 21778326‚ 17187232‚ 18164969‚ 18497957‚ 16631465‚ 26898890‚ 27621404‚ 28652578‚ 26837699‚ 27803004‚ 31050087‚ 30233647 Comment: show Variant summary: ATM c.1066-6T>G alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. Although the variant was reported to be associated with a partial splicing defect (see e.g. Broeks_2000, Dork_2001, Fang_2010), several patient samples were also reported to have second-site mutations that could also affect splicing, therefor the splicing effect of the variant in isolation is currently unclear (Tavtigian_2009, Fievet_2019). The variant allele was found at a frequency of 0.0014 in 270694 control chromosomes, predominantly within the Non-Finnish European subpopulation at a frequency of 0.0024 in the gnomAD database (including 2 homozygotes). The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 2.4 fold of the estimated maximal expected allele frequency for a pathogenic variant in ATM causing Breast Cancer phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. In addition, the variant was reported to be found in the FLOSSIES database in 33/7325 European American women, who were older than age 70 years and have never had cancer. The allele frequency in this cohort is also higher than expected for a pathogenic variant in ATM causing Breast Cancer (0.0023 vs. 0.001), further supporting a benign role for the variant. Though the variant has been reported in the literature in homozygous individuals affected with Ataxia Telangiectasia (A-T), these patients carried second-site mutations that were sufficient to explain the A-T phenotype (Tavtigian_2009, Fievet_2019). The variant was also reported in compound heterozygosity, with (potential) pathogenic ATM variants in trans, in an individual affected with breast cancer (Fang_2010) and also in a patient with multiple myeloma and (per authors) an atypical, milder A-T phenotype (Austen_2008). Therefore these reports do not support the association of the variant with A-T. The variant, c.1066-6T>G, also has been reported in the literature in individuals affected with Breast Cancer, however in most of the cases co-occurrence and/or co-segregation data was not provided, therefore these reports do not provide unequivocal conclusions about association of the variant with Breast Cancer. Moreover, in case-control studies the variant did not have significantly increased risk association with breast cancer (Dork_2001, Bernstein_2006, Ding_2011). One recent case-control study reported the variant with an increased risk for CLL (OR: 3.29), however this analysis had a relatively small sample size and most patients were sporadic cases, thus this risk association might not be reliable (Tiao 2017). Twelve other submitters have provided clinical-significance assessments for this variant in ClinVar after 2014 (without evidence for independent evaluation), and classified the variant as VUS (4x), likely benign (3x) / benign (5x). Based on the evidence outlined above, the variant was classified as benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown |
| Uncertain significance (Jun 13, 2019) N Not contributing to aggregate classification | criteria provided, single submitter (ACMG Guidelines, 2015) | Familial cancer of breast | Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV001428726.1 First in ClinVar: Aug 16, 2020 Last updated: Aug 16, 2020 | Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1 |
| Benign (Dec 10, 2020) N Not contributing to aggregate classification | criteria provided, single submitter (ACMG Guidelines, 2015) | Hereditary cancer-predisposing syndrome | Color Diagnostics, LLC DBA Color Health Accession: SCV000687286.2 First in ClinVar: Feb 19, 2018 Last updated: Jun 19, 2021 | Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Platform type: NGS |
| Benign (Mar 18, 2021) N Not contributing to aggregate classification | criteria provided, single submitter (ACMG Guidelines, 2015) | not specified | Genetic Services Laboratory, University of Chicago Accession: SCV000593476.2 First in ClinVar: Aug 27, 2017 Last updated: Jan 29, 2022 | Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no |
| Benign (Nov 06, 2020) N Not contributing to aggregate classification | criteria provided, single submitter (Sema4 Curation Guidelines) | Hereditary cancer-predisposing syndrome | Sema4, Sema4 Accession: SCV002529707.1 First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 | Observation: 1 Collection method: curation Allele origin: germline Affected status: unknown Observation 1 Collection method: curation Allele origin: germline Affected status: unknown |
| Likely benign (Jul 02, 2018) N Not contributing to aggregate classification | criteria provided, single submitter (Mendelics Assertion Criteria 2017) | Ataxia-telangiectasia syndrome | Mendelics Accession: SCV000838482.2 First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 | Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown |
| Likely benign (Nov 05, 2021) N Not contributing to aggregate classification | criteria provided, single submitter (ACMG Guidelines, 2015) | Familial cancer of breast Ataxia-telangiectasia syndrome | Fulgent Genetics, Fulgent Genetics Accession: SCV002805757.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 | Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown |
| Benign (Jan 27, 2023) N Not contributing to aggregate classification | criteria provided, single submitter (Quest Diagnostics criteria) | not provided | Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV004219908.1 First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 | Publications: PubMed (38) PubMed: 15101044‚ 15880680‚ 22146522‚ 27067391‚ 23091097‚ 18164969‚ 15450731‚ 14643952‚ 17351744‚ 16631465‚ 21792198‚ 11839094‚ 11173867‚ 26898890‚ 26250988‚ 12810666‚ 17393301‚ 28652578‚ 28779002‚ 15217508‚ 19781682‚ 21933854‚ 20544271‚ 20678261‚ 11996792‚ 14562025‚ 12673794‚ 10677309‚ 35716007‚ 32918381‚ 30549301‚ 27803004‚ 31050087‚ 30233647‚ 11606401‚ 11830610‚ 16958054‚ 18497957 Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown |
| Likely benign (Jun 23, 2023) N Not contributing to aggregate classification | criteria provided, single submitter (ACMG Guidelines, 2015) | Breast and/or ovarian cancer | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Accession: SCV002042283.3 First in ClinVar: Dec 29, 2021 Last updated: Feb 04, 2024 | Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown |
| Benign (Feb 04, 2025) N Not contributing to aggregate classification | criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) | Ataxia-telangiectasia syndrome | Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000153826.16 First in ClinVar: Jun 09, 2014 Last updated: Feb 25, 2025 | Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown |
| Uncertain significance (Sep 16, 2014) N Not contributing to aggregate classification | criteria provided, single submitter (EGL Classification Definitions 2015) | not provided | Eurofins Ntd Llc (ga) Accession: SCV000232903.6 First in ClinVar: Jun 29, 2015 Last updated: Apr 13, 2025 | Publications: PubMed (4) PubMed: 10677309‚ 11606401‚ 19781682‚ 20544271 Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ATM Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 1 Zygosity: Single Heterozygote Sex: mixed |
| Likely benign (Oct 01, 2025) N Not contributing to aggregate classification | criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) | not provided | CeGaT Center for Human Genetics Tuebingen Accession: SCV000574904.41 First in ClinVar: May 08, 2017 Last updated: Dec 14, 2025 | Comment: show ATM: PP3, BS2 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 38 |
| Benign (Feb 27, 2017) N Not contributing to aggregate classification | criteria provided, single submitter (ACMG Guidelines, 2015) | not specified | PreventionGenetics, part of Exact Sciences Accession: SCV000805489.1 First in ClinVar: Sep 13, 2018 Last updated: Sep 13, 2018 | Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown |
| Benign (Aug 20, 2018) N Not contributing to aggregate classification | criteria provided, single submitter (Athena Diagnostics Criteria) | not provided | Athena Diagnostics Accession: SCV000840913.1 First in ClinVar: May 08, 2017 Last updated: May 08, 2017 | Publications: PubMed (32) PubMed: 15101044‚ 15880680‚ 22146522‚ 27067391‚ 23091097‚ 18164969‚ 15450731‚ 14643952‚ 17351744‚ 16631465‚ 21792198‚ 11839094‚ 11173867‚ 26898890‚ 26250988‚ 12810666‚ 17393301‚ 28652578‚ 28779002‚ 15217508‚ 19781682‚ 21933854‚ 20544271‚ 20678261‚ 11996792‚ 14562025‚ 12673794‚ 10677309‚ 11606401‚ 11830610‚ 16958054‚ 18497957 Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown |
| Uncertain significance (Apr 28, 2017) N Not contributing to aggregate classification | criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) | Ataxia-telangiectasia syndrome | Illumina Laboratory Services, Illumina Accession: SCV001263699.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020 | Publications: PubMed (4) PubMed: 11606401‚ 21933854‚ 19781682‚ 15880680 Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown |
| Likely benign (Jun 05, 2021) N Not contributing to aggregate classification | criteria provided, single submitter (GeneDx Variant Classification Process June 2021) | Not Provided | GeneDx Accession: SCV000149041.8 First in ClinVar: May 17, 2014 Last updated: Apr 09, 2018 | Comment: show This variant is associated with the following publications: (PMID: 26898890, 28779002, 28643015, 21933854, 10677309, 15101044, 11606401, 25040471, 27067391, 26250988, 18573109, 26662178, 27798748, 27296296, 19781682, 16958054, 27803004, 28627265, 28691344, 16914028, 28652578, 20544271, 30549301, 11830610, 32918381) (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes |
| Likely benign (Nov 03, 2021) N Not contributing to aggregate classification | criteria provided, single submitter (ACMG Guidelines, 2015) | not provided | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden Accession: SCV002010849.3 First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 | Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: not provided Observation 1 Collection method: clinical testing Allele origin: germline Affected status: not provided |
| Benign (Nov 01, 2023) N Not contributing to aggregate classification | criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) | not provided | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000602558.5 First in ClinVar: Sep 28, 2017 Last updated: Feb 20, 2024 | Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown |
| Likely benign (May 09, 2019) N Not contributing to aggregate classification | criteria provided, single submitter (Ambry Variant Classification Scheme 2023) | Hereditary cancer-predisposing syndrome | Ambry Genetics Accession: SCV000183798.6 First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 | Publications: PubMed (7) PubMed: 10677309‚ 11606401‚ 15101044‚ 15880680‚ 19781682‚ 20544271‚ 21933854 Comment: show This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown |
| Benign (-) N Not contributing to aggregate classification | criteria provided, single submitter (ACMG Guidelines, 2015) | not provided (Autosomal recessive inheritance) | Breakthrough Genomics, Breakthrough Genomics Accession: SCV005230998.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 | Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes |
| Benign (Mar 04, 2025) N Not contributing to aggregate classification | criteria provided, single submitter (ACMG Guidelines, 2015) | not specified | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV002760518.4 First in ClinVar: Dec 17, 2022 Last updated: Mar 11, 2025 | Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown |
| Likely benign (Apr 15, 2025) N Not contributing to aggregate classification | criteria provided, single submitter (ACMG Guidelines, 2015) | Not provided | Mayo Clinic Laboratories, Mayo Clinic Accession: SCV004226227.2 First in ClinVar: Jan 06, 2024 Last updated: Apr 20, 2025 | Comment: show BS1, BP2_mod (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 6 |
| Benign (Jan 16, 2025) N Not contributing to aggregate classification | criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023)) | Familial cancer of breast | Myriad Genetics, Inc. Accession: SCV005083829.2 First in ClinVar: Jul 23, 2024 Last updated: Jun 22, 2025 | Publications: PubMed (1) PubMed: 25085752 Comment: show This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown |
| Uncertain significance (Dec 30, 2019) N Not contributing to aggregate classification | criteria provided, single submitter (ACGS Best Practice Guidelines for Variant Classification in Rare Disease 2020) | Intellectual disability | Cambridge Genomics Laboratory, East Genomic Laboratory Hub, NHS Genomic Medicine Service Accession: SCV006306877.1 First in ClinVar: Aug 16, 2025 Last updated: Aug 16, 2025 | Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1 Clinical Features: Hypertelorism (present) , Delayed speech and language development (present) , Intellectual disability (present) , Global developmental delay (present) , Delayed gross motor development (present) , Attention deficit hyperactivity disorder (present) , Abnormal hair whorl (present) , Delayed fine motor development (present) |
| Likely benign (-) N Not contributing to aggregate classification | no assertion criteria provided | not provided | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001968518.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 | Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes |
| Likely benign (Oct 30, 2019) N Not contributing to aggregate classification | no assertion criteria provided | Ataxia-telangiectasia | Natera, Inc. Accession: SCV002092668.1 First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 | Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown |
| Uncertain significance (Nov 01, 2006) N Not contributing to aggregate classification | no assertion criteria provided | RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE | OMIM Accession: SCV000023336.4 First in ClinVar: Apr 04, 2013 Last updated: Sep 18, 2016 | Publications: PubMed (4) PubMed: 10677309‚ 9792409‚ 12673794‚ 16958054 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: This variant, formerly titled ATAXIA-TELANGIECTASIA and BREAST CANCER, SUSCEPTIBILITY TO, has been reclassified because its contribution to either phenotype has not been confirmed. In a … (more) This variant, formerly titled ATAXIA-TELANGIECTASIA and BREAST CANCER, SUSCEPTIBILITY TO, has been reclassified because its contribution to either phenotype has not been confirmed. In a series of 82 Dutch patients who had developed breast cancer (114480) under the age of 45 years and had survived 5 years or more, Broeks et al. (2000) identified 3 who carried a splice site mutation of the ATM gene, a T-to-G transversion at position -6 of the 3-prime splice acceptor site of intron 10. They stated that this mutation had not been detected in a small series of Dutch patients with ataxia-telangiectasia (AT; 208900) (Broeks et al., 1998). However, they pointed to a German patient with AT who was homozygous for this mutation. Broeks et al. (2003) genotyped a number of polymorphic markers in and around the ATM locus in 18 samples from different populations carrying the IVS10-6T-G mutation: 17 unrelated breast cancer patients who were heterozygous for the mutation and a single AT patient who was homozygous. The same markers were also genotyped among 39 unrelated healthy individuals without this mutation. Haplotype analyses revealed one common ancestor in all mutation carriers. By means of a maximum likelihood method, they estimated the age of this mutation to be approximately 2,000 generations. They concluded that the mutation occurred only once during human evolution, at least 50,000 years ago. They predicted that this mutation could be widely distributed across Europe and probably the Middle East and Western Asia. In a population-based study, Bernstein et al. (2006) found no association between the IVS10-6T-G allele and increased risk of breast cancer. The allele was identified in 13 (0.3%) of 3,757 patients and 10 (0.8%) of 1,268 controls. (less) |
| Uncertain significance (Feb 14, 2018) N Not contributing to aggregate classification | no assertion criteria provided | Hereditary cancer-predisposing syndrome | True Health Diagnostics Accession: SCV000787840.1 First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 | Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown |
| Likely benign (-) N Not contributing to aggregate classification | no assertion criteria provided | Malignant tumor of breast | Department of Pathology and Laboratory Medicine, Sinai Health System Additional submitter: Franklin by Genoox Study: The Canadian Open Genetics Repository (COGR) Accession: SCV001550381.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 | Comment: show The ATM c.1066-6T>G variant was identified in 51 of 18,694 proband chromosomes (frequency: 0.003) from individuals or families with chronic lymphocatic leukemia, breast or ovarian cancer and was present in 70 of 27,754 control chromosomes (frequency: 0.003) from healthy individuals (Ding 2010, Tiao 2017). The variant was identified in dbSNP (rs201686625) as “with other allele”, ClinVar (classified as uncertain significance by Ambry Genetics, Integrated Genetics and 5 other submitters; as benign by Invitae, Color, Athena Diagnostics and 2 other submitters; and as likely benign by GeneDx and 2 other submitters) and LOVD 3.0 (observed 8x). The variant was identified in control databases in 357 of 266,346 chromosomes (2 homozygous) at a frequency of 0.001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 7 of 23,658 chromosomes (freq: 0.0003), Other in 2 of 6198 chromosomes (freq: 0.0003), Latino in 19 of 32,652 chromosomes (freq: 0.0006), European in 286 of 123,010 chromosomes (freq: 0.002), Finnish in 18 of 25,254 chromosomes (freq: 0.0007), and South Asian in 25 of 27,738 chromosomes (freq: 0.0009); it was not observed in the Ashkenazi Jewish or East Asian populations. The variant was identified by our laboratory in multiple patients with pathogenic variants in BRCA2 (including c.1929del, p.Arg645Glufs*15 and c.755_758del, p.Asp252Valfs*24). The variant was also identified in the homozygous state in a patient with ataxia telangiectasia (Dork 2001), for whom alternate pathogenic variants were subsequently identified (Tavtigian 2009). A patient with mild ataxia telangiectasia was found to carry this variant in the compound heterozygous state and had reduced ATM protein expression and kinase activity, indicating this variant does not fully abolish protein expression and function (Austen 2016). Additionally, this variant leads to an increase in exon 11 skipping, although some exon 11 skipping is found in controls who do not carry this variant (Soukupova 2007). The c.1066-6T>G variant is located in the 3' splice region and does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence; variants involving these positions sometimes affect splicing and 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: yes Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: yes |
| Uncertain significance (Sep 27, 2021) N Not contributing to aggregate classification | no assertion criteria provided | Hereditary cancer-predisposing syndrome | Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. Accession: SCV001977066.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 Comment: splice_region_variant | Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown |
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Minigene-based splicing analysis and ACMG/AMP-based tentative classification of 56 ATM variants. | Bueno-Martínez E | The Journal of pathology | 2022 | PMID: 35716007 |
| Evidence of pathogenicity for the leaky splice variant c.1066-6T>G in ATM. | Schröder S | American journal of medical genetics. Part A | 2020 | PMID: 32918381 |
| Functional classification of ATM variants in ataxia-telangiectasia patients. | Fiévet A | Human mutation | 2019 | PMID: 31050087 |
| Genotype, extrapyramidal features, and severity of variant ataxia-telangiectasia. | Schon K | Annals of neurology | 2019 | PMID: 30549301 |
| Computational Tools for Splicing Defect Prediction in Breast/Ovarian Cancer Genes: How Efficient Are They at Predicting RNA Alterations? | Moles-Fernández A | Frontiers in genetics | 2018 | PMID: 30233647 |
| Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks. | Decker B | Journal of medical genetics | 2017 | PMID: 28779002 |
| Rare germline variants in ATM are associated with chronic lymphocytic leukemia. | Tiao G | Leukemia | 2017 | PMID: 28652578 |
| Mismatch-repair-deficient metastatic pancreatic ductal adenocarcinoma with a germline PALB2 mutation: unusual genetics, unusual clinical course. | Boeck S | Annals of oncology : official journal of the European Society for Medical Oncology | 2017 | PMID: 27803004 |
| Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing. | Balmaña J | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2016 | PMID: 27621404 |
| A unified analytic framework for prioritization of non-coding variants of uncertain significance in heritable breast and ovarian cancer. | Mucaki EJ | BMC medical genomics | 2016 | PMID: 27067391 |
| Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking Known BRCA Mutations. | Caminsky NG | Human mutation | 2016 | PMID: 26898890 |
| Clinical impact of clonal and subclonal TP53, SF3B1, BIRC3, NOTCH1, and ATM mutations in chronic lymphocytic leukemia. | Nadeu F | Blood | 2016 | PMID: 26837699 |
| Protein-truncating variants in moderate-risk breast cancer susceptibility genes: a meta-analysis of high-risk case-control screening studies. | Aloraifi F | Cancer genetics | 2015 | PMID: 26250988 |
| Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes. | Pruss D | Breast cancer research and treatment | 2014 | PMID: 25085752 |
| Biallelic ATM inactivation significantly reduces survival in patients treated on the United Kingdom Leukemia Research Fund Chronic Lymphocytic Leukemia 4 trial. | Skowronska A | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2012 | PMID: 23091097 |
| Severe reaction to radiotherapy for breast cancer as the presenting feature of ataxia telangiectasia. | Byrd PJ | British journal of cancer | 2012 | PMID: 22146522 |
| ATM germline heterozygosity does not play a role in chronic lymphocytic leukemia initiation but influences rapid disease progression through loss of the remaining ATM allele. | Skowronska A | Haematologica | 2012 | PMID: 21933854 |
| Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours. | Reiman A | British journal of cancer | 2011 | PMID: 21792198 |
| Functional characterization connects individual patient mutations in ataxia telangiectasia mutated (ATM) with dysfunction of specific DNA double-strand break-repair signaling pathways. | Keimling M | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 2011 | PMID: 21778326 |
| Mutations in BRCA2 and PALB2 in male breast cancer cases from the United States. | Ding YC | Breast cancer research and treatment | 2011 | PMID: 20927582 |
| Lack of association between ATM C.1066-6T > G mutation and breast cancer risk: a meta-analysis of 8,831 cases and 4,957 controls. | Ding H | Breast cancer research and treatment | 2011 | PMID: 20544271 |
| Low levels of ATM in breast cancer patients with clinical radiosensitivity. | Fang Z | Genome integrity | 2010 | PMID: 20678261 |
| Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer. | Tavtigian SV | American journal of human genetics | 2009 | PMID: 19781682 |
| Pathogenic ATM mutations occur rarely in a subset of multiple myeloma patients. | Austen B | British journal of haematology | 2008 | PMID: 18573109 |
| Contribution of mutations in ATM to breast cancer development in the Czech population. | Soukupova J | Oncology reports | 2008 | PMID: 18497957 |
| Detection of ATM gene mutations in young lung cancer patients: a population-based control study. | Schneider J | Archives of medical research | 2008 | PMID: 18164969 |
| The spectrum of ATM missense variants and their contribution to contralateral breast cancer. | Broeks A | Breast cancer research and treatment | 2008 | PMID: 17393301 |
| ATM allelic variants associated to hereditary breast cancer in 94 Chilean women: susceptibility or ethnic influences? | Tapia T | Breast cancer research and treatment | 2008 | PMID: 17351744 |
| Mutation analysis of five candidate genes in familial breast cancer. | Marsh A | Breast cancer research and treatment | 2007 | PMID: 17187232 |
| Population-based estimates of breast cancer risks associated with ATM gene variants c.7271T>G and c.1066-6T>G (IVS10-6T>G) from the Breast Cancer Family Registry. | Bernstein JL | Human mutation | 2006 | PMID: 16958054 |
| ATM alterations in childhood non-Hodgkin lymphoma. | Gumy-Pause F | Cancer genetics and cytogenetics | 2006 | PMID: 16631465 |
| Two ATM variants and breast cancer risk. | Thompson D | Human mutation | 2005 | PMID: 15880680 |
| Breast cancer in female carriers of ATM gene alterations: outcome of adjuvant radiotherapy. | Meyer A | Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology | 2004 | PMID: 15450731 |
| Frequency of the ATM IVS10-6T-->G variant in Australian multiple-case breast cancer families. | Lindeman GJ | Breast cancer research : BCR | 2004 | PMID: 15217508 |
| Functional consequences of ATM sequence variants for chromosomal radiosensitivity. | Gutiérrez-Enríquez S | Genes, chromosomes & cancer | 2004 | PMID: 15101044 |
| Clinical radiosensitivity in breast cancer patients carrying pathogenic ATM gene mutations: no observation of increased radiation-induced acute or late effects. | Bremer M | Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology | 2003 | PMID: 14643952 |
| ATM variants 7271T>G and IVS10-6T>G among women with unilateral and bilateral breast cancer. | Bernstein JL | British journal of cancer | 2003 | PMID: 14562025 |
| Contributions of ATM mutations to familial breast and ovarian cancer. | Thorstenson YR | Cancer research | 2003 | PMID: 12810666 |
| IVS10-6T>G, an ancient ATM germline mutation linked with breast cancer. | Broeks A | Human mutation | 2003 | PMID: 12673794 |
| Elevated frequency of ATM gene missense mutations in breast cancer relative to ethnically matched controls. | Sommer SS | Cancer genetics and cytogenetics | 2002 | PMID: 11996792 |
| Radiosensitivity of ataxia telangiectasia and Nijmegen breakage syndrome homozygotes and heterozygotes as determined by three-color FISH chromosome painting. | Neubauer S | Radiation research | 2002 | PMID: 11839094 |
| Dominant negative ATM mutations in breast cancer families. | Chenevix-Trench G | Journal of the National Cancer Institute | 2002 | PMID: 11830610 |
| Spectrum of ATM gene mutations in a hospital-based series of unselected breast cancer patients. | Dörk T | Cancer research | 2001 | PMID: 11606401 |
| Mutagen sensitivity of human lymphoblastoid cells with a BRCA1 mutation in comparison to ataxia telangiectasia heterozygote cells. | Speit G | Cytogenetics and cell genetics | 2000 | PMID: 11173867 |
| ATM-heterozygous germline mutations contribute to breast cancer-susceptibility. | Broeks A | American journal of human genetics | 2000 | PMID: 10677309 |
| ATM germline mutations in classical ataxia-telangiectasia patients in the Dutch population. | Broeks A | Human mutation | 1998 | PMID: 9792409 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ATM | - | - | - | - |
| https://erepo.clinicalgenome.org/evrepo/ui/interpretation/bccd9f16-4086-4c14-8d78-04c52ad58630 | - | - | - | - |
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Submissions - Functional Data
functionally abnormal -- retained intron assessed by RNAseq Result: junction spanning - intron inclusion with mutation (p=0.0) Modifies a natural acceptor site at NC_000011.9:g.108119659 from 11.28 to 8.13 bits. Significant p-values: junction spanning - intron inclusion with mutation (1 reads, p=0.0). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification. Citation: PubMed: 31275557 Dr. Peter K. Rogan Lab, Western University Accession: SCV006761029.1 Submitted: 2025-10-17 Assay description:In the sample (TCGA-B6-A0IO), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)
- Disease context: Familial cancer of breast
- Transcript: NM_000051.4:c.1066-6T>G
- Molecular phenotype measured: splicing
- Cell line: TCGA-B6-A0IO
- Tissue: Breast Invasive Carcinoma (BRCA)
- Collection method: in vitro
- Species: human
- Number of controls: 502
In the sample (TCGA-AB-2895), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)
- Disease context: Acute myeloid leukemia
- Transcript: NM_000051.4:c.1066-6T>G
- Molecular phenotype measured: splicing
- Cell line: TCGA-AB-2895
- Tissue: Acute Myeloid Leukemia (LAML)
- Collection method: in vitro
- Species: human
- Number of controls: 255
In the sample (TCGA-AB-2830), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)
- Disease context: Acute myeloid leukemia
- Transcript: NM_000051.4:c.1066-6T>G
- Molecular phenotype measured: splicing
- Cell line: TCGA-AB-2830
- Tissue: Acute Myeloid Leukemia (LAML)
- Collection method: in vitro
- Species: human
- Number of controls: 255
In the sample (TCGA-AB-2963), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)
- Disease context: Acute myeloid leukemia
- Transcript: NM_000051.4:c.1066-6T>G
- Molecular phenotype measured: splicing
- Cell line: TCGA-AB-2963
- Tissue: Acute Myeloid Leukemia (LAML)
- Collection method: in vitro
- Species: human
- Number of controls: 255
In the sample (TCGA-C5-A2LS), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)
- Disease context: Cervical cancer
- Transcript: NM_000051.4:c.1066-6T>G
- Molecular phenotype measured: splicing
- Cell line: TCGA-C5-A2LS
- Tissue: Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC)
- Collection method: in vitro
- Species: human
- Number of controls: 226
In the sample (TCGA-BR-A4PF), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)
- Disease context: Gastric cancer
- Transcript: NM_000051.4:c.1066-6T>G
- Molecular phenotype measured: splicing
- Cell line: TCGA-BR-A4PF
- Tissue: Stomach Adenocarcinoma (STAD)
- Collection method: in vitro
- Species: human
- Number of controls: 621
Text-mined citations for rs201686625 ...
Help These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.Record last updated Dec 14, 2025
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.
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