title: The BRCA2 genetic variant IVS7 + 2T-->G is a mutation.
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.
authors.affiliation: Myriad Genetic Laboratories, Salt Lake City, UT 84108, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Pyne
authors.forename: A R
authors.initials: AR
authors.lastname: Brothman
authors.forename: B
authors.initials: B
authors.lastname: Ward
authors.forename: D
authors.initials: D
authors.lastname: Pruss
authors.forename: B C
authors.initials: BC
authors.lastname: Hendrickson
authors.forename: T
authors.initials: T
authors.lastname: Scholl
mesh_terms: D020121:5' Untranslated Regions; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007438:Introns; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012326:RNA Splicing; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors