ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5474C>T (p.Ala1825Val) (rs397507352)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222134 SCV000274539 likely benign Hereditary cancer-predisposing syndrome 2018-05-10 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
GeneDx RCV001281723 SCV000517308 likely benign not provided 2019-10-14 criteria provided, single submitter clinical testing
Invitae RCV000457281 SCV000549687 likely benign Hereditary breast and ovarian cancer syndrome 2020-08-31 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001281723 SCV000600641 likely benign not provided 2020-07-20 criteria provided, single submitter clinical testing
Counsyl RCV000031549 SCV000784866 uncertain significance Breast-ovarian cancer, familial 2 2017-01-18 criteria provided, single submitter clinical testing
Color Health, Inc RCV000222134 SCV000911760 benign Hereditary cancer-predisposing syndrome 2017-02-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000420987 SCV001554633 likely benign not specified 2021-03-22 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.5474C>T (p.Ala1825Val) 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 2.9e-05 in 273532 control chromosomes (gnomAD and publication). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. In a large case-control association study the variant was not detected in any of the breast cancer cases but was detected in controls, and was assigned a classification of Benign (Momozawa_2018). Furthermore, a recent publication involving the ENIGMA network of collaborators (Parsons_2019) assigned a classification of Likely Benign based on likelihood ratios (LRs) for pathogenicity estimated from clinical data of co-occurrence, family history and bioinformatic predictions. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign and one ClinVar submitter (evaluation after 2014) cites it as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Research and Development, ARUP Laboratories RCV001642373 SCV001854838 likely benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
Sharing Clinical Reports Project (SCRP) RCV000031549 SCV000054154 benign Breast-ovarian cancer, familial 2 2012-03-27 no assertion criteria provided clinical testing

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