Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000636238 | SCV000757670 | pathogenic | Familial cancer of breast; Fanconi anemia complementation group J | 2018-01-05 | criteria provided, single submitter | clinical testing | This variant is an in-frame deletion of the genomic region encompassing exons 7-16 of the BRIP1 gene. It preserves the integrity of the reading frame. While this particular variant has not been reported in the literature, other copy number variants that delete a subset of exons 7-16, while also preserving the integrity of the reading frame, have been reported in individuals with ovarian cancer (PMID: 26720728), and have been classified as pathogenic (PMID: 16973432, 16116424, Invitae). This sequence change removes nearly all of the iron-sulfur (Fe-S) cluster binding domain of BRIP1, including two of the four conserved cysteine residues (PMID: 16973432). It also removes the alanine residue at codon 349, which is disrupted in an individual with Fanconi anemia (PMID: 16116424), and is predicted to abolish BRIP1 helicase activity (PMID: 16973432). These results indicate that domain encodes a necessary part of the BRIP1 gene product. For these reasons, this variant has been classified as Pathogenic. |