A biochemical analysis demonstrates that the BRCA1 intronic variant IVS10-2A--> C is a mutation.

Sequence analysis of cDNA from an asymptomatic patient belonging to a high-risk breast cancer family carrying the genetic variant BRCA1 IVS10-2A-->C revealed that functional BRCA1 mRNA was derived from only one of the patient's chromosomes. The other chromosome produced an aberrant RNA splicing transcript that deleted exon 11. Analysis of the patient's genomic DNA demonstrated that the chromosome producing the non-functional mRNA carried the genotype BRCA1 IVS10-2A-->C. This transversion disrupts a highly conserved base in the consensus splice acceptor motif. These results support the conclusion that BRCA1 IVS10-2A-->C is a mutation that confers predisposition to breast and ovarian cancer.