Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002364241 | SCV002659237 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-18 | criteria provided, single submitter | clinical testing | The p.V2174I variant (also known as c.6520G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 6520. The valine at codon 2174 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
University of Washington Department of Laboratory Medicine, |
RCV002364241 | SCV003852600 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004999714 | SCV005624503 | uncertain significance | not provided | 2024-08-08 | criteria provided, single submitter | clinical testing | The BRCA2 c.6520G>A (p.Val2174Ile) variant has been reported to be located in a region of the BRCA2 gene that is tolerant to missense sequence changes (PMID: 31911673 (2020)). To the best of our knowledge, this variant has not been reported in individuals with BRCA2-related disorders. This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |