ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4949A>G (p.Asn1650Ser) (rs55870064)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000120142 SCV000149109 likely benign not specified 2017-11-07 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 RCV001082738 SCV000166113 benign Ataxia-telangiectasia syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000115200 SCV000212953 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000120142 SCV000334654 benign not specified 2015-08-28 criteria provided, single submitter clinical testing
Color RCV000115200 SCV000682231 benign Hereditary cancer-predisposing syndrome 2015-04-13 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000120142 SCV000694294 likely benign not specified 2019-07-18 criteria provided, single submitter clinical testing Variant summary: ATM c.4949A>G (p.Asn1650Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00059 in 256842 control chromosomes, predominantly at a frequency of 0.0073 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 7.3 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 East Asian origin. c.4949A>G has been reported in the literature in individuals affected with Breast Cancer (Tavtigian_2009, Bernstein_2010), Tung_2015, Xie_2018) . These data indicate that the variant may be associated with disease. However, the variant has also been observed within healthy control populations (Tavtigian_2009, Shi_2011). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in >50%-90% of normal activity (Takagi_2004). Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Athena Diagnostics Inc RCV000589659 SCV000840943 likely benign not provided 2017-12-20 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000589659 SCV001249806 likely benign not provided 2019-10-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001082738 SCV001264587 likely benign Ataxia-telangiectasia syndrome 2017-04-27 criteria provided, single submitter clinical testing 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ITMI RCV000120142 SCV000084282 not provided not specified 2013-09-19 no assertion provided reference population
True Health Diagnostics RCV000115200 SCV000787867 likely benign Hereditary cancer-predisposing syndrome 2017-08-22 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.