Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164578 | SCV000215236 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-03 | criteria provided, single submitter | clinical testing | The p.F3146S variant (also known as c.9437T>C), located in coding exon 24 of the BRCA2 gene, results from a T to C substitution at nucleotide position 9437. The phenylalanine at codon 3146 is replaced by serine, an amino acid with highly dissimilar properties. This variant was non-functional in a homology-directed DNA repair (HDR) assay (Richardson ME et al. Am J Hum Genet, 2021 03;108:458-468). 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. |
| Labcorp Genetics |
RCV001071583 | SCV001236893 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-08-05 | 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 3146 of the BRCA2 protein (p.Phe3146Ser). 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: 185206). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33609447) indicates that this missense variant is expected to disrupt BRCA2 function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BRCA2 function (PMID: 33609447, 35736817). 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. |
| Center for Genomic Medicine, |
RCV003493471 | SCV004243081 | uncertain significance | not specified | 2025-03-04 | criteria provided, single submitter | clinical testing | |
| Clinical Genetics Laboratory, |
RCV004696861 | SCV005197334 | uncertain significance | not provided | 2023-11-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004696861 | SCV005201999 | likely pathogenic | not provided | 2023-12-19 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Not observed in large population cohorts (gnomAD); Also known as 9665T>C; This variant is associated with the following publications: (PMID: 12228710, 33609447, 35736817) |