ClinVar

Description

This gross deletion results in the loss of amino acids 307-374. This removes nearly all of the iron-sulfur (Fe-S) cluster binding domain of BRIP1, including two of the four conserved cysteine residues within that domain (PMID: 16973432). Also, this deletion removes the Ala349 amino acid, which has been shown to be mutated in a patient with Fanconi anemia (PMID: 16116424), and is predicted to abolish BRIP1 helicase activity (PMID: 16973432). These results indicate that this exon encodes a necessary part of the BRIP1 gene product. This sequence change is a gross deletion of the genomic region including exon 8 of the BRIP1 gene. This deletion removes a portion of intron 7 and extends through the first 203 nucleotides of exon 8 (c.918+2790_1121del). Since this deletion removes the exon 8 splice acceptor site and the majority of exon 8, the exact effect of this variant on the BRIP1 protein cannot be determined. It is possible that an in-frame deletion may be generated that encompasses the entire exon 8 due to exon skipping . Alternatively, since the 3' breakpoint of the deletion lies within codon 374 of the BRIP1 protein, a frameshift could be generated, thus creating a premature translational stop signal which would be expected to result in an absent or disrupted protein product. In the absence of knowing the exact effect of this variant on the BRIP1 protein, this variant has been classified as Likely Pathogenic.