Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000636237 | SCV000757669 | pathogenic | Familial cancer of breast; Fanconi anemia complementation group J | 2021-08-02 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 8-14 of the BRIP1 gene. This variant would be expected to be in-frame, preserving the integrity of the reading frame. This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant disrupts the conserved ATPase-Helicase domain, including the iron-sulfur (Fe-S) cluster of the BRIP1 protein, which is important for DNA helicase activity of BRIP1 (PMID: 11301010, 21345144, 33619228). While functional studies have not been performed to directly test the effect of this variant on BRIP1 protein function, this suggests that disruption of this region of the protein is causative of disease. This variant disrupts a region of the BRIP1 protein in which other variant(s) (p.Ala349Pro) have been determined to be pathogenic (PMID: 16116424, 16973432, 20639400, 24448499, 27107905). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |