Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000129332 | SCV000184095 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-29 | criteria provided, single submitter | clinical testing | The p.P3150L variant (also known as c.9449C>T), located in coding exon 24 of the BRCA2 gene, results from a C to T substitution at nucleotide position 9449. The proline at codon 3150 is replaced by leucine, an amino acid with similar properties. This alteration had an intermediate functional effect in a homology-directed DNA repair assay (Hart SN et al. Genet. Med., 2019 01;21:71-80). This alteration has not been reported in 7051 unselected female breast cancer patients and with a carrier frequency of 0.00009 in 11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This alteration has not been reported in 7636 unselected prostate cancer patients and with a carrier frequency of 0.00016 in 12366 male controls of Japanese ancestry (Momozawa Y et al. J Natl Cancer Inst, 2020 Apr;112:369-376). 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 |
RCV001340379 | SCV001534187 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 3150 of the BRCA2 protein (p.Pro3150Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 10923033, 21520333). ClinVar contains an entry for this variant (Variation ID: 126212). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BRCA2 function (PMID: 29884841). 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. |
| Breast Cancer Information Core |
RCV000114108 | SCV000147637 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-06-20 | no assertion criteria provided | clinical testing |