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

J Hum Genet. 2000;45(6):351-7. doi: 10.1007/s100380070007.

Abstract

Biochemical and genetic characterizations that support the conclusion that the variant BRCA2 IVS7 + 2T --> G represents a deleterious mutation are presented. 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 chromosome that does not produce the normal mRNA. Additionally, an RNA splicing 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 amino acids before terminating with an opal stop codon. The experimental approach presented produces strong evidence of the presence of a deleterious mutation, because the contribution by both chromosomes to each RNA species analyzed was tracked using a coding region polymorphism as a marker. Furthermore, a single nucleotide polymorphism (SNP) haplotype analysis that confirms the location of the intronic variant and an associated family history that shows a high incidence of cancer supported these biochemical data.

MeSH terms

  • 5' Untranslated Regions
  • BRCA2 Protein
  • Breast Neoplasms / genetics*
  • Exons
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation / genetics*
  • Haplotypes
  • Humans
  • Introns
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • RNA Splicing
  • Transcription Factors / genetics*

Substances

  • 5' Untranslated Regions
  • BRCA2 Protein
  • Neoplasm Proteins
  • Transcription Factors