ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.10024G>A (p.Glu3342Lys) (rs28897761)

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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 RCV000220854 SCV000274258 uncertain significance Hereditary cancer-predisposing syndrome 2015-03-05 criteria provided, single submitter clinical testing
Color RCV000220854 SCV000911853 likely benign Hereditary cancer-predisposing syndrome 2018-01-03 criteria provided, single submitter clinical testing
GeneDx RCV000445222 SCV000526510 likely benign not specified 2016-12-13 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.
Integrated Genetics/Laboratory Corporation of America RCV000586827 SCV000694487 uncertain significance not provided 2017-08-24 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.10024G>A (p.Glu3342Lys) variant involves the alteration of a conserved nucleotide. 4/5 in silico tools predict a damaging outcome for this variant, however these have not been investigated by functional studies. This variant is absent in 120890 control chromosomes. This variant has been reported in individuals affected with breast/ovarian cancer without strong evidence for a causative role (Alsop 2012, Azzollini 2016). In one publication, the variant is cited to co-occur with a pathgoenic BRCA1/2 variant, however the exact variant was not specified (Alsop_2012). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as VUS, until additional information becomes available.
Invitae RCV000463710 SCV000549705 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-05-13 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 3342 of the BRCA2 protein (p.Glu3342Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with ovarian cancer and in an independent  family affected with breast and/or ovarian cancer (PMID: 22711857, 27062684). ClinVar contains an entry for this variant (Variation ID: 37718). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000031299 SCV000053904 likely benign Breast-ovarian cancer, familial 2 2009-04-15 no assertion criteria provided clinical testing

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