Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000167402 | SCV000218257 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-02 | criteria provided, single submitter | clinical testing | The p.Q827K variant (also known as c.2479C>A), located in coding exon 16 of the BRIP1 gene, results from a C to A substitution at nucleotide position 2479. The glutamine at codon 827 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV000167402 | SCV000909763 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-05 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with lysine at codon 827 of the BRIP1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 BRIP1-related disorders 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. |
| Labcorp Genetics |
RCV001850368 | SCV002110918 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-11-08 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is not present in population databases (gnomAD no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 187654). This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 827 of the BRIP1 protein (p.Gln827Lys). 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. |