Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000509591 | SCV000608063 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-30 | criteria provided, single submitter | clinical testing | The p.L2904F variant (also known as c.8710C>T), located in coding exon 20 of the BRCA2 gene, results from a C to T substitution at nucleotide position 8710. The leucine at codon 2904 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration had an indeterminate readout in a mouse ESC-based assay in which authors calculated a functional score based on cell viability and drug sensitivity (Biswas K et al. Cell Rep Methods, 2023 Nov;3:100628). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV001232737 | SCV001405305 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2025-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 2904 of the BRCA2 protein (p.Leu2904Phe). 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: 441418). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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. |
| Genetic Services Laboratory, |
RCV001821427 | SCV002066835 | uncertain significance | not specified | 2021-01-25 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003159128 | SCV003853011 | uncertain significance | not provided | 2023-04-03 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 8938C>T; This variant is associated with the following publications: (PMID: 12228710) |