ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7651A>C (p.Lys2551Gln) (rs398122587)

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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 RCV000132265 SCV000187348 likely benign Hereditary cancer-predisposing syndrome 2017-11-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign)
GeneDx RCV000160246 SCV000210661 likely benign not specified 2018-02-20 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 RCV000589630 SCV000695090 uncertain significance not provided 2016-04-04 criteria provided, single submitter clinical testing Variant Summary: The c.7651A>C variant involves the alteration of a non-conserved nucleotide and 4/4 in silico tools predict a neutral outcome. The variant is absent from the large, broad ExAC control population. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Multiple reputable clinical labs have classified the variant as "likely benign", without evidence to independently evaluate. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000476389 SCV000549845 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-02 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamine at codon 2551 of the BRCA2 protein (p.Lys2551Gln). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 91488). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160246 SCV000600763 uncertain significance not specified 2016-12-03 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077005 SCV000108802 likely benign Breast-ovarian cancer, familial 2 2012-01-11 no assertion criteria provided clinical testing

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