A BRCA2 mutation incorrectly mapped in the original BRCA2 reference sequence, is a common West Danish founder mutation disrupting mRNA splicing

Research output: Contribution to journalArticle


Inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose carriers to breast and ovarian cancer. The authors have identified a mutation in BRCA2, 7845+1G > A (c.7617+1G > A), not previously regarded as deleterious because of incorrect mapping of the splice junction in the originally published genomic reference sequence. This reference sequence is generally used in many laboratories and it maps the mutation 16 base pairs inside intron 15. However, according to the recent reference sequences the mutation is located in the consensus donor splice sequence. By reverse transcriptase analysis, loss of exon 15 in the final transcript interrupting the open reading frame was demonstrated. Furthermore, the mutation segregates with a cancer phenotype in 18 Danish families. By genetic analysis of more than 3,500 Danish breast/ovarian cancer risk families, the mutation was identified as the most common BRCA2 mutation in West Denmark, while it is rare in Central and East Denmark and not identified in South Sweden. Haplotype analysis using dense SNP arrays indicated a common founder of the mutation approximately 1,500 years ago.


  • Mads Thomassen
  • Inge Sokilde Pedersen
  • Ida Vogel
  • Thomas v. O. Hansen
  • Charlotte Brasch-Andersen
  • Claus L. Brasen
  • Dorthe Cruger
  • Lone Sunde
  • Finn C. Nielsen
  • Uffe B. Jensen
  • Marie Luise Bisgaard
  • Åke Borg
  • Anne-Marie Gerdes
  • Torben A. Kruse
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology


  • Hereditary breast cancer, BRCA2, 7845+1G > A, Founder mutation, Mutation age, SNP array, RT-PCR
Original languageEnglish
Pages (from-to)179-185
JournalBreast Cancer Research and Treatment
Issue number1
Publication statusPublished - 2011
Publication categoryResearch