Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000215166 | SCV000274961 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-08-10 | criteria provided, single submitter | clinical testing | The p.D847N variant (also known as c.2539G>A), located in coding exon 17 of the BRIP1 gene, results from a G to A substitution at nucleotide position 2539. The aspartic acid at codon 847 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly 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 |
RCV000538746 | SCV000633620 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2017-05-02 | criteria provided, single submitter | clinical testing | In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 231192). This sequence change replaces aspartic acid with asparagine at codon 847 of the BRIP1 protein (p.Asp847Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. |