Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001524778 | SCV001734729 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-11-03 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 20 of the BRIP1 gene, creating a premature translation stop signal in the last coding exon. This variant is expected to escape nonsense-mediated decay and be expressed as a truncated protein with disrupted functional domains involved in BRCA1-binding and DNA damage and replication stress response (PMID: 11301010, 14983014, 20159562, 20173781, 22792074). Although functional studies have not been reported for this variant, this variant is expected to impair critical BRIP1 protein function. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRIP1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic. |