Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000043850 | SCV000071863 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-09-12 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 547 of the BRCA2 protein (p.Ser547Leu). 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: 51163). 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) performed at Invitae indicates that this missense variant is not expected to disrupt 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. |
| Ambry Genetics | RCV002399403 | SCV002707695 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-29 | criteria provided, single submitter | clinical testing | The p.S547L variant (also known as c.1640C>T), located in coding exon 9 of the BRCA2 gene, results from a C to T substitution at nucleotide position 1640. The serine at codon 547 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is well 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, |
RCV002399403 | SCV003851541 | 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). |
| Breast Cancer Information Core |
RCV000112946 | SCV000145903 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2001-10-29 | no assertion criteria provided | clinical testing |