The BRCA2 genetic variant IVS7+2T -> G is a mutation

Biochemical and genetic characterizations that support the conclusion that the variant BRCA2 IVS7 + 2T --> G represents a deleterious mutation are pre sented. RNA analysis from a breast cancer patient with BRCA2 IVS7 + 2T --> G showed that the productive message was produced from only one chromosome. A haplotype analysis confirmed that the intronic variant resides on the ch romosome that does not produce the normal mRNA. Additionally, an RNA splici ng product that deletes exon 7 was produced by the chromosome that carries BRCA2 IVS7 + 2T --> G. The deletion of exon 7 from the RNA alters the open reading frame by removing residues 249-287 and incorporating 18 abnormal am ino acids before terminating with an oral stop codon. The experimental appr oach presented produces strong evidence of the presence of a deleterious mu tation, because the contribution by both chromosomes to each RNA species an alyzed was tracked using a coding region polymorphism as a marker. Furtherm ore, a single nucleotide polymorphism (SNP) haplotype analysis that confirm s the location of the intronic variant and an associated family history tha t shows a high incidence of cancer supported these biochemical data.