Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001025964 | SCV001188254 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-30 | criteria provided, single submitter | clinical testing | The p.N2348S variant (also known as c.7043A>G), located in coding exon 13 of the BRCA2 gene, results from an A to G substitution at nucleotide position 7043. The asparagine at codon 2348 is replaced by serine, an amino acid with highly similar properties. This amino acid position is not 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. |
Labcorp Genetics |
RCV001216628 | SCV001388433 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-06-05 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 2348 of the BRCA2 protein (p.Asn2348Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs747817752, ExAC 0.01%). This variant has not been reported in the literature in individuals with BRCA2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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, |
RCV003493780 | SCV004243057 | likely benign | not specified | 2025-03-04 | criteria provided, single submitter | clinical testing |