ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2584A>G (p.Lys862Glu) (rs80356927)

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Total submissions: 10
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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) RCV000031057 SCV000244324 benign Breast-ovarian cancer, familial 1 2015-08-10 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 = 0.00000991
Invitae RCV000047887 SCV000075900 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-06 criteria provided, single submitter clinical testing
GeneDx RCV000074574 SCV000108659 likely benign not specified 2017-11-03 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.
Ambry Genetics RCV000162978 SCV000213466 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
Color RCV000162978 SCV000537503 likely benign Hereditary cancer-predisposing syndrome 2015-11-25 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000074574 SCV000593691 likely benign not specified 2017-04-13 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758799 SCV000887646 likely benign not provided 2018-03-27 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000074574 SCV000918734 likely benign not specified 2018-06-14 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2584A>G (p.Lys862Glu) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.1e-05 in 276828 control chromosomes (in gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (6.1e-05 vs 0.001), allowing no conclusion about variant significance. c.2584A>G has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five 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. Multiple databases as well as publications citing multifactorial probability based models have classified the variant as benign/likely benign (Easton 2007, Lindor 2012). Based on the evidence outlined above, the variant was classified as likely benign.
Sharing Clinical Reports Project (SCRP) RCV000031057 SCV000053652 benign Breast-ovarian cancer, familial 1 2010-02-10 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031057 SCV000144481 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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