ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.2494C>T (p.Arg832Cys)

gnomAD frequency: 0.00025  dbSNP: rs2229022
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 14
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129082 SCV000183785 likely benign Hereditary cancer-predisposing syndrome 2018-05-18 criteria provided, single submitter clinical testing Co-occurence with mutation in same gene (phase unknown);In silico models in agreement (benign)
GeneDx RCV000211982 SCV000209704 likely benign not specified 2017-10-02 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000199664 SCV000254070 likely benign Ataxia-telangiectasia syndrome 2021-12-15 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000211982 SCV000593499 uncertain significance not specified 2016-09-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000211982 SCV000694227 likely benign not specified 2021-07-19 criteria provided, single submitter clinical testing Variant summary: ATM c.2494C>T (p.Arg832Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00023 in 278644 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in ATM causing Breast Cancer (0.00023 vs 0.001), allowing no conclusion about variant significance. Multiple publications have cited the variant in affected individuals with varying phenotypes including Lynch syndrome, breast cancer, chronic lymphocytic leukemia, prostate cancer and pancreatic cancer (e.g. Grant_2015, Nadeu_2016, Schwartz_2019, Skowronska_2012, Paulo_2018, Tung_2016, Yurgelun_2015) but also in controls (e.g. Momozawa_2018, Tavtigian_2009). These reports do not provide unequivocal conclusions about association of the variant with Breast Cancer. A co-occurrence with a pathogenic variant has been reported following internal testing (SMAD4 c.787+2T>C). A ClinVar submitter reports co-occurrence with another mutation in the ATM gene (phase unknown) for the phenotype of Hereditary cancer-predisposing syndrome (SCV000183785.6). Furthermore, the variant was reported in the FLOSSIES database in 5 women older than age 70 years who have never had cancer. Altogether, these data provide supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Ten ClinVar submitters (evaluation after 2014) cite the variant as likely benign (n=6) and as uncertain significance (n=4). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics,PreventionGenetics RCV000587618 SCV000805517 uncertain significance not provided 2014-04-10 criteria provided, single submitter clinical testing
GeneKor MSA RCV000129082 SCV000821791 likely benign Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Mendelics RCV000199664 SCV000838507 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000129082 SCV000902655 likely benign Hereditary cancer-predisposing syndrome 2015-04-24 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV000199664 SCV001262551 uncertain significance Ataxia-telangiectasia syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001762286 SCV002010839 uncertain significance Familial cancer of breast 2021-11-03 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000129082 SCV002532222 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-22 criteria provided, single submitter curation
True Health Diagnostics RCV000129082 SCV000805213 likely benign Hereditary cancer-predisposing syndrome 2018-05-08 no assertion criteria provided clinical testing
Natera, Inc. RCV000199664 SCV001461091 uncertain significance Ataxia-telangiectasia syndrome 2020-04-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.