Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001222893 | SCV001395015 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-05-22 | 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 present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 715 of the BRIP1 protein (p.His715Arg). 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. 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. ClinVar contains an entry for this variant (Variation ID: 951059). |
| Prevention |
RCV003398964 | SCV004111338 | uncertain significance | BRIP1-related condition | 2022-12-29 | criteria provided, single submitter | clinical testing | The BRIP1 c.2144A>G variant is predicted to result in the amino acid substitution p.His715Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-59821906-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |