Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000636142 | SCV000757574 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2022-03-15 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 839 of the BRIP1 protein (p.Trp839Arg). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: 530331). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. |
Color Diagnostics, |
RCV000773235 | SCV000906847 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces tryptophan with arginine at codon 839 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. |