Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002450059 | SCV002682235 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-28 | criteria provided, single submitter | clinical testing | The p.W31R variant (also known as c.91T>A), located in coding exon 2 of the BRCA2 gene, results from a T to A substitution at nucleotide position 91. The tryptophan at codon 31 is replaced by arginine, an amino acid with dissimilar properties. p.W31R (encoded by this variant, c.91T>A, as well as a different nucleotide substitution at this position, c.91T>C) has been described in the literature as resulting in impaired PALB2 binding and BRCA2-associated homology directed repair activity (Xia B et al. Mol. Cell. 2006 Jun;22:719-29; Biswas K et al. Hum. Mol. Genet. 2012 Sep;21:3993-4006; Al Abo M et al. Cancer Res. 2014 Feb;74(3):797-807; Biswas K et al. NPJ Genom Med. 2020 Dec;5(1):52; Thomassen M et al. Hum Mutat. 2022 Dec;43(12):1921-1944). It has also been reported to disrupt a key residue in the BRCA2-PALB2 interaction interface (Oliver AW et al. EMBO Rep. 2009 Sep;10(9):990-6; Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |