Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001914851 | SCV002138796 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-09-03 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with phenylalanine at codon 93 of the BRCA2 protein (p.Ser93Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. 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. 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. This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002440964 | SCV002748295 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-08 | criteria provided, single submitter | clinical testing | The p.S93F variant (also known as c.278C>T), located in coding exon 2 of the BRCA2 gene, results from a C to T substitution at nucleotide position 278. The serine at codon 93 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |