Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001032383 | SCV001195690 | likely pathogenic | Familial cancer of breast; Fanconi anemia complementation group J | 2022-04-21 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 6 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 nuclear localization signal (NLS) of the BRIP1 protein, which is necessary for translocation to the nucleus (PMID: 19379763, 12569564). 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. |