Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000561737 | SCV000668936 | likely benign | Hereditary cancer-predisposing syndrome | 2023-12-07 | 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. |
| Color Diagnostics, |
RCV000561737 | SCV001344826 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-07-02 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with proline at codon 241 of the BRIP1 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/251174 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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 |
RCV001227266 | SCV001399618 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-11-09 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 241 of the BRIP1 protein (p.Ser241Pro). This variant is present in population databases (rs771542690, gnomAD 0.01%). This missense change has been observed in individual(s) with prostate cancer, as well as unaffected controls (PMID: 31214711). ClinVar contains an entry for this variant (Variation ID: 483181). 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. |
| Gene |
RCV001194705 | SCV002004253 | uncertain significance | not provided | 2021-02-01 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in prostate cancer cases but also in healthy controls (Momozawa 2019); This variant is associated with the following publications: (PMID: 31214711) |
| Leiden Open Variation Database | RCV001194705 | SCV001364465 | uncertain significance | not provided | 2019-08-13 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa. |