Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Sema4, |
RCV002257010 | SCV002531410 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-02-02 | criteria provided, single submitter | curation | |
| Gene |
RCV003329439 | SCV004036779 | likely pathogenic | not provided | 2023-03-23 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |
| Myriad Genetics, |
RCV003336512 | SCV004044379 | pathogenic | Familial cancer of breast | 2023-06-06 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
| Invitae | RCV003774762 | SCV004591222 | pathogenic | Familial cancer of breast; Fanconi anemia complementation group J | 2023-06-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1691984). 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). This sequence change creates a premature translational stop signal (p.Glu795*) in the BRIP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRIP1 are known to be pathogenic (PMID: 16116423, 17033622, 21964575). |
| Laboratory for Molecular Medicine, |
RCV004017912 | SCV004848796 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2022-11-03 | criteria provided, single submitter | clinical testing | The p.Glu795X variant in BRIP1 has not been reported in individuals with breast and or ovarian cancer and was absent from lrge population studies. This nonsense variant leads to a premature termination codon at position 795, which is predicted to lead to a truncated or absent protein. Loss of function of the BRIP1 gene is an established disease mechanism in autosomal dominant breast and ovariant cancer. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant breast and ovarian cancer. ACMG/AMP Criteria applied: PVS1, PM2_Supporting. |