Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000572464 | SCV000673163 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2017-04-07 | criteria provided, single submitter | clinical testing | The c.3173_3179delTGACAGTinsCTC variant, located in coding exon 19 of the BRIP1 gene, results from the deletion of 7 nucleotides and insertion of 3 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.L1058Pfs*19). Premature stop codons are typically deleterious in nature, however, this stop codon occurs at the 3' terminus of BRIP1, is not expected to trigger nonsense-mediated mRNA decay, and removes the last 171 amino acids of the protein. The exact functional impact of these removed amino acids is unknown at this time; however, the C-terminal region of the protein has been shown by structural, biochemical, and mutational analysis to be relevant for the protein function (Leung CC et al. J. Biol. Chem. 2011 Feb; 286(6):4292-301. Xie J et al. PLoS Genet. 2012 Jul; 8(7):e1002786; Gong Z et al. Mol. Cell, 2010 Feb;37:438-46). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |