Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV003300652 | SCV003998342 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-04-20 | criteria provided, single submitter | clinical testing | The p.W2619G pathogenic mutation (also known as c.7855T>G), located in coding exon 16 of the BRCA2 gene, results from a T to G substitution at nucleotide position 7855. The tryptophan at codon 2619 is replaced by glycine, an amino acid with highly dissimilar properties. This alteration is non-functional in a homology-directed DNA repair (HDR) assay (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. Based on internal structural assessment, this alteration will result in destabilization of the structure at the HD/OBD1 interface (Yang H et al. Science, 2002 Sep;297:1837-48). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is considered a disease-causing mutation. |