Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001187262 | SCV001353999 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-25 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with threonine at codon 1066 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). 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 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 |
RCV001219207 | SCV001391132 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2019-04-14 | criteria provided, single submitter | clinical testing | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRIP1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with threonine at codon 1066 of the BRIP1 protein (p.Ser1066Thr). The serine residue is weakly conserved and there is a small physicochemical difference between serine and threonine. |
| Sema4, |
RCV001187262 | SCV002533682 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-25 | criteria provided, single submitter | curation | |
| Ambry Genetics | RCV001187262 | SCV005552963 | likely benign | Hereditary cancer-predisposing syndrome | 2024-06-26 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |