The silent mutation nucleotide 744 G --> A, Lys172Lys, in exon 6 of BRCA2 results in exon skipping

Breast Cancer Res Treat. 2010 Feb;119(3):547-50. doi: 10.1007/s10549-009-0359-4. Epub 2009 Mar 8.


Germ-line mutations in BRCA2 predispose to breast and ovarian cancer. Mutations are widespread throughout the gene and include disease-causing mutations as frameshift, nonsense, splicing mutations and large genomic rearrangements. However a large number of mutations, including missense, silent and intron variants are of unknown significance. Here, we describe the functional characterization of a silent mutation (nucleotide 744 G --> A/c.516 G --> A, Lys172Lys) in exon 6 of BRCA2 in a Danish family with breast and ovarian cancer. Exon trapping analysis showed that the mutation results in skipping of exon 6 and/or both exon 5 and 6, which was verified by RT-PCR analysis on RNA isolated from whole blood of the affected patient. We therefore conclude that the BRCA2 silent mutation Lys172Lys is a disease-causing mutation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / genetics*
  • Breast Neoplasms, Male / genetics
  • Chromatography, High Pressure Liquid
  • Exons / genetics
  • Female
  • Genes, BRCA2*
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Ovarian Neoplasms / genetics
  • Pedigree
  • Reverse Transcriptase Polymerase Chain Reaction