Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000130050 | SCV000184877 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-10-10 | criteria provided, single submitter | clinical testing | The p.N851K variant (also known as c.2553T>G), located in coding exon 17 of the BRIP1 gene, results from a T to G substitution at nucleotide position 2553. The asparagine at codon 851 is replaced by lysine, an amino acid with similar properties. This amino acid position is poorly 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 |
RCV003764865 | SCV004595803 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-04-13 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 BRIP1 protein function. ClinVar contains an entry for this variant (Variation ID: 141495). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 851 of the BRIP1 protein (p.Asn851Lys). |