ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.452T>C (p.Val151Ala) (rs730881503)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000663051 SCV000786101 uncertain significance Breast-ovarian cancer, familial 2 2018-02-21 criteria provided, single submitter clinical testing
GeneDx RCV000160021 SCV000210240 uncertain significance not provided 2018-02-12 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.452T>C at the cDNA level, p.Val151Ala (V151A) at the protein level, and results in the change of a Valine to an Alanine (GTA>GCA). Using alternate nomenclature, this variant would be defined as BRCA2 680T>C. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Val151Ala was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Val151Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000474713 SCV000549776 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-09-20 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 151 of the BRCA2 protein (p.Val151Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs730881503, ExAC 0.01%) but has not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 182175). 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 variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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