ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4828G>A (p.Val1610Met) (rs80358705)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044498 SCV000072511 benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000074530 SCV000108615 likely benign not specified 2018-02-21 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.
Ambry Genetics RCV000130783 SCV000185676 likely benign Hereditary cancer-predisposing syndrome 2018-10-31 criteria provided, single submitter clinical testing In silico models in agreement (benign);Co-occurence with mutation in same gene (phase unknown)
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000074530 SCV000591929 uncertain significance not specified 2014-01-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000074530 SCV000694805 likely benign not specified 2019-08-16 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.4828G>A (p.Val1610Met) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.6e-05 in 250074 control chromosomes, predominantly at a frequency of 0.00021 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (9.6e-05 vs 0.00075), allowing no conclusion about variant significance. c.4828G>A has been reported in the literature in individuals affected with Breast and Ovarian Cancer (Lee_2008, Kote-Jarai_2011, Simard_2007, Caminsky_2016, Jarhelle_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. At-least two known co-occurrences with other pathogenic variant(s) have been reported (UMD database-BRCA1 c.4327C>T, p.Arg1443*; BIC database-BRCA1 c.3481_3491delGAAGATACTAG, p.Glu1161_Ser1164?fs), providing supporting evidence for a benign role. 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. Four have classified the variant as Benign/Likely Benign and one has classified the variant as uncertain significance citing overlapping references utilized in this evaluation. Based on the evidence outlined above, the variant was re-classified as likely benign.
Color RCV000130783 SCV000910745 benign Hereditary cancer-predisposing syndrome 2017-01-25 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001112023 SCV001269637 uncertain significance Fanconi anemia, complementation group D1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV000031508 SCV001269638 uncertain significance Breast-ovarian cancer, familial 2 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Sharing Clinical Reports Project (SCRP) RCV000031508 SCV000054113 benign Breast-ovarian cancer, familial 2 2009-08-31 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031508 SCV000146488 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Department of Medical Genetics, University Hospital of North Norway RCV000031508 SCV000301448 uncertain significance Breast-ovarian cancer, familial 2 2016-05-01 no assertion criteria provided clinical testing

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