ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1730C>T (p.Ala577Val) (rs876661280)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000215464 SCV000279970 uncertain significance not provided 2016-03-08 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.1730C>T at the cDNA level, p.Ala577Val (A577V) at the protein level, and results in the change of an Alanine to a Valine (GCA>GTA). Using alternate nomenclature, this variant would be defined as BRCA2 1958C>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Ala577Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Alanine and Valine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Ala577Val occurs at a position that is not conserved and is not located in a known functional domain (UniProt). Protein-based in silico analyses predict that this variant is unlikely to alter protein structure or function, while multiple splicing models predict that this variant results in the creation of a new cryptic splice donor site. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. Based on currently available evidence, it is unclear whether BRCA2 Ala577Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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