ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7966C>G (p.Leu2656Val)

dbSNP: rs2072748978
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002413843 SCV002675748 uncertain significance Hereditary cancer-predisposing syndrome 2020-05-29 criteria provided, single submitter clinical testing The p.L2656V variant (also known as c.7966C>G), located in coding exon 16 of the BRCA2 gene, results from a C to G substitution at nucleotide position 7966. The leucine at codon 2656 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001358346 SCV001554051 uncertain significance Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Leu2656Val variant was not identified in the literature nor was it identified in the following databases: dbSNP, ClinVar, COGR, Cosmic, MutDB, LOVD 3.0, UMD-LSDB, BIC Database, ARUP Laboratories, Zhejiang University, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Leu2656 residue is conserved across mammals and other organisms, and 4 of 5 computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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