Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001026701 | SCV001189132 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-16 | criteria provided, single submitter | clinical testing | The p.F2560S variant (also known as c.7679T>C), located in coding exon 15 of the BRCA2 gene, results from a T to C substitution at nucleotide position 7679. The phenylalanine at codon 2560 is replaced by serine, 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. |
| Color Diagnostics, |
RCV001026701 | SCV001734017 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-08-04 | criteria provided, single submitter | clinical testing | This missense variant replaces phenylalanine with serine at codon 2560 of the BRCA2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251294 chromosomes 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. |
| Gene |
RCV001776089 | SCV002013481 | uncertain significance | not provided | 2024-06-24 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in an individual undergoing whole genome sequencing (PMID: 33726816); Also known as 7907T>C; This variant is associated with the following publications: (PMID: 28431939, 33726816) |
| Labcorp Genetics |
RCV001873415 | SCV002173072 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2560 of the BRCA2 protein (p.Phe2560Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 827190). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Baylor Genetics | RCV003473604 | SCV004211856 | uncertain significance | Familial cancer of breast | 2023-10-16 | criteria provided, single submitter | clinical testing |