Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000132321 | SCV000187407 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-30 | criteria provided, single submitter | clinical testing | The p.S2701P variant (also known as c.8101T>C), located in coding exon 17 of the BRCA2 gene, results from a T to C substitution at nucleotide position 8101. The serine at codon 2701 is replaced by proline, an amino acid with similar properties. This amino acid position is poorly 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. |
Labcorp Genetics |
RCV000695361 | SCV000823856 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-01-26 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with proline at codon 2701 of the BRCA2 protein (p.Ser2701Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 142869). 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. |
Color Diagnostics, |
RCV000132321 | SCV000906775 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-09 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with proline at codon 2701 of the BRCA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |