ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5402G>A (p.Gly1801Asp) (rs531210457)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132269 SCV000187352 likely benign Hereditary cancer-predisposing syndrome 2019-07-26 criteria provided, single submitter clinical testing In silico models in agreement (benign);Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
GeneDx RCV000160007 SCV000210218 likely benign not specified 2017-04-04 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 RCV000461010 SCV000549327 benign Hereditary breast and ovarian cancer syndrome 2020-11-23 criteria provided, single submitter clinical testing
Color Health, Inc RCV000132269 SCV000910793 benign Hereditary cancer-predisposing syndrome 2016-06-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000160007 SCV001337979 benign not specified 2021-01-30 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5402G>A (p.Gly1801Asp) results in a non-conservative amino acid change located in the BRCT domain (IPR001357) of 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 2.4e-05 in 251420 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.5402G>A has been reported in the literature in individuals affected with breast and ovarian cancer (e.g. Mehta_2018, Manie_2016) and as an unclassified variant in at-least two relatives of patients with early-onset breast cancer (Juwle_2012) without strong evidence of causality. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. At least two publications report experimental evidence evaluating an impact on homology directed repair (HDR) activity (example, Lu_2015, Findlay_2018). Both studies no impact of this variant on HDR activity. Four 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 benign.
Brotman Baty Institute,University of Washington RCV001073171 SCV001238682 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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