Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000707847 | SCV000836957 | likely pathogenic | Familial cancer of breast; Fanconi anemia complementation group J | 2022-10-08 | criteria provided, single submitter | clinical testing | This variant results in a copy number gain of the genomic region encompassing exon(s) 7-10 of the BRIP1 gene. While the exact position of this variant cannot be determined from the data, sub-genic copy number gains are generally in tandem (PMID: 25640679). This variant is predicted to be in-frame, and likely preserves the integrity of the reading frame. A similar copy number variant has been observed in individual(s) with breast cancer and ovarian cancer (Invitae). It has also been observed to segregate with disease in related individuals. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |