Description
This duplication of one nucleotide in BRCA2 is denoted c.9633dupA at the cDNA level and p.Gly3212ArgfsX10 (G3212RfsX10) at the protein level. The normal sequence, with the base that is duplicated in braces, is GTAC[A]GGAA. The duplication causes a frameshift which changes a Glycine to an Arginine at codon 3212, and creates a premature stop codon at position 10 of the new reading frame. While this variant is not expected to lead to nonsense-mediated decay, it is predicted to cause loss of normal protein function through protein truncation. BRCA2 c.9633dupA is expected to result in the loss of the nuclear localization signals 1 and 2 (NLS1/NLS2) and the Cyclin A and RAD51 binding domains (Esashi 2005, Borg 2010, Roy 2012). Using alternate nomenclature, this variant would be defined as BRCA2 9861dupA. This duplication has not, to our knowledge, been reported in the literature. Based on the currently available evidence, we consider BRCA2 c.9633dupA to be a likely pathogenic variant.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
