Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001186182 | SCV001352533 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-18 | criteria provided, single submitter | clinical testing | This missense variant replaces cysteine with glycine at codon 1081 of the BRCA2 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV001186182 | SCV002609471 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-23 | criteria provided, single submitter | clinical testing | The p.C1081G variant (also known as c.3241T>G), located in coding exon 10 of the BRCA2 gene, results from a T to G substitution at nucleotide position 3241. The cysteine at codon 1081 is replaced by glycine, an amino acid with highly dissimilar properties. This amino acid position is poorly 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, |
RCV001186182 | SCV003851795 | 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). |