Hereditary breast cancer and the clinical significance of variants in the BRCA1 and BRCA2 genes


In 15% of DNA tests for hereditary breast/ovarian cancer a clinical uncertain variant is identified in the BRCA1/2 genes. This test result causes psychological distress in families and makes clinical management problematic. My project aims to improve classification and optimize guidelines for communication by means of integrated and translational approaches.


Scientific article

  • S. Moghadasi, N. Hofland, J.N. Wouts, F.B. Hogervorst, J.T. Wijnen, M.P.G. Vreeswijk, C.J. van Asperen(2013): Variants of Uncertain Significance in BRCA1 and BRCA2. assessment of in silico analysis and a proposal for communication in genetic counselling. Journal of Medical Genetics pp. 74 - 79 ISSN: 0022-2593.
  • S. Moghadasi(2016): Classification and Clinical Management of Variants of Uncertain Significance in High Penetrance Cancer Predisposition Genes. Hum Mutat. 2016 Apr;37(4):331-6. doi: 10.1002/humu.22956. Epub 2016 Feb 5. Review. pp. 331 - 336
  • S. Moghadasi(2017): The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium. J Med Genet. 2017 May 10. pii: jmedgenet-2017-104560. doi: 10.1136/jmedgenet-2017-104560. [Epub ahead of print] pp. - - -
  • S. Moghadasi, H. Shimelis(2017): BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer. Cancer Res. 2017 Jun 1;77(11):2789-2799. doi: 10.1158/0008-5472.CAN-16-2568. Epub 2017 Mar 10. pp. 2789 - 2799
  • S. Moghadasi(2017): Performance of BRCA1/2 mutation prediction models in male breast cancer patients Genet. 2017 Jun 6. [Epub ahead of print] pp. - - -


Project number


Main applicant

S. Moghadasi

Affiliated with

Universiteit Leiden, Leids Universitair Medisch Centrum, Klinisch Genetisch Centrum

Team members

S. Moghadasi


01/10/2011 to 19/01/2018