ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7887G>T (p.Trp2629Cys)

dbSNP: rs886040734
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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 RCV000572889 SCV000668586 uncertain significance Hereditary cancer-predisposing syndrome 2015-12-12 criteria provided, single submitter clinical testing The p.W2629C variant (also known as c.7887G>T), located in coding exon 16 of the BRCA2 gene, results from a G to T substitution at nucleotide position 7887. The tryptophan at codon 2629 is replaced by cysteine, an amino acid with highly dissimilar 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 RCV000501119 SCV000592156 uncertain significance Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Trp2629Cys variant was not identified in the literature, nor was it identified in the dbSNP, NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC), LOVD, COSMIC, ClinVar, Clinvitae, ARUP Laboratories BRCA Mutations Database, GeneInsight COGR, BIC or UMD. The p.Trp2629 residue is conserved across mammals and other organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the Cys 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 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% chance that the variant creates a cryptic 5’ splice donor site and one predicts a greater than 10% chance that the variant creates a cryptic 3’ splice acceptor site. 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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