ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5198A>G (p.Asp1733Gly) (rs80357270)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112560 SCV001161598 benign Breast-ovarian cancer, familial 1 2019-06-18 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000577
Invitae RCV001088030 SCV000076867 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129798 SCV000184607 likely benign Hereditary cancer-predisposing syndrome 2018-09-11 criteria provided, single submitter clinical testing Intact protein function observed in appropriate functional assay(s)
GeneDx RCV000417372 SCV000209987 likely benign not specified 2018-02-14 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000417372 SCV000699212 likely benign not specified 2019-11-27 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5198A>G (p.Asp1733Gly) results in a non-conservative amino acid change located in the BRCT domain (IPR001357) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251488 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.5198A>G has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (e.g. Judkins_2005, Tavtigian_2006). These reports however, do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrence with other pathogenic variants (such as BRCA1 c.1059G>A, p.Trp353Ter) have been reported in the BIC database and in publication (Tavtigian_2006), providing supporting evidence for a benign role. In addition, multiple functional studies report comparable transcriptional activity and other properties between the variant and wild-type. Five other ClinVar submitters cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590656 SCV000888942 likely benign not provided 2020-01-24 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129798 SCV000903063 benign Hereditary cancer-predisposing syndrome 2015-11-09 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112560 SCV000145389 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000112560 SCV001242875 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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