ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1144A>C (p.Lys382Gln) (rs371454630)

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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 RCV000130560 SCV000185431 likely benign Hereditary cancer-predisposing syndrome 2017-08-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Co-occurence with mutation in same gene (phase unknown)
Invitae RCV000195524 SCV000254168 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-06-04 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamine at codon 382 of the BRCA2 protein (p.Lys382Gln). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamine. This variant is present in population databases (rs371454630, ExAC <0.01%). This variant has been reported in individuals in the Universal Mutation Database (PMID: 22144684). However, it occurs with a pathogenic variant in BRCA2 in one individual. While it is unknown if these variants are on the same or opposite chromosomes, this observation suggests that the c.1144A>C variant is not a primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 141867). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this is a rare missense change that is not predicted to affect protein function or cause disease. However, the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000500188 SCV000591729 uncertain significance not specified 2014-01-17 criteria provided, single submitter clinical testing
Color RCV000130560 SCV000688695 likely benign Hereditary cancer-predisposing syndrome 2017-03-27 criteria provided, single submitter clinical testing
GeneDx RCV000500188 SCV000730719 likely benign not specified 2017-03-13 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.
Sharing Clinical Reports Project (SCRP) RCV000238792 SCV000297501 likely benign Breast-ovarian cancer, familial 2 2014-04-03 no assertion criteria provided clinical testing

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