Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000467513 | SCV000547330 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 416 of the BRIP1 protein (p.Arg416Gln). This variant is present in population databases (rs772570870, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 407842). 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 with a negative predictive value of 80%. 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. |
| Ambry Genetics | RCV000566468 | SCV000661475 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-20 | criteria provided, single submitter | clinical testing | The p.R416Q variant (also known as c.1247G>A), located in coding exon 8 of the BRIP1 gene, results from a G to A substitution at nucleotide position 1247. The arginine at codon 416 is replaced by glutamine, 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. |
| Color Diagnostics, |
RCV000566468 | SCV001349806 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-09 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 416 of the BRIP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 been identified in 1/251142 chromosomes 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. |
| Gene |
RCV001584151 | SCV001820854 | uncertain significance | not provided | 2019-10-14 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |