ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.10082A>C (p.Gln3361Pro) (rs751250810)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570247 SCV000661456 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000570247 SCV000903252 likely benign Hereditary cancer-predisposing syndrome 2016-02-23 criteria provided, single submitter clinical testing
GeneDx RCV000487297 SCV000564805 likely benign not specified 2017-07-13 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.
Invitae RCV000536779 SCV000635128 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-04-06 criteria provided, single submitter clinical testing This sequence change replaces glutamine with proline at codon 3361 of the BRCA2 protein (p.Gln3361Pro). The glutamine residue is weakly conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is present in population databases (rs751250810, ExAC 0.05%), including a homozygous individual, and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 418092). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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