ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1810A>G (p.Lys604Glu) (rs80358467)

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Total submissions: 11
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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) RCV000031341 SCV001161608 benign Breast-ovarian cancer, familial 2 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 = 0.000415
Ambry Genetics RCV000129177 SCV000183912 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Invitae RCV001084993 SCV000283176 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000031341 SCV000488958 uncertain significance Breast-ovarian cancer, familial 2 2016-07-26 criteria provided, single submitter clinical testing
GeneDx RCV000425351 SCV000512342 likely benign not specified 2017-12-21 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.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000425351 SCV000591771 uncertain significance not specified 2013-01-11 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000425351 SCV000694569 likely benign not specified 2019-10-22 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.1810A>G (p.Lys604Glu) results in a 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 240642 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1810A>G has been reported in the literature in individuals affected with Breast and Ovarian Cancer. These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer (Ritterhouse_2016, Zuntini_2018). Co-occurrences with other pathogenic variants have been reported (BRCA1 c.5263_5264insC, p.Ser1755?fs; BRCA1 c.68_69delAG, p.Glu23fsX17), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (3x benign/likely benign, 1x VUS). Based on the evidence outlined above, the variant was classified as likely benign.
Color RCV000129177 SCV000902945 benign Hereditary cancer-predisposing syndrome 2016-11-16 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590202 SCV001133695 likely benign not provided 2019-03-15 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031341 SCV000053946 benign Breast-ovarian cancer, familial 2 2009-11-18 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031341 SCV000145947 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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