Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study



Determination of mutation status of BRCA1 and BRCA2 has become part of the clinical routine. However, the spectrum of genetic variants differs between populations. The aim of this study was to deliver a comprehensive description of all detected variants.


In families fulfilling one of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) criteria for genetic testing, one affected was chosen for analysis. DNA of blood lymphocytes was amplified by PCR and prescreened by DHPLC. Aberrant fragments were sequenced. All coding exons and splice sites of BRCA1 and BRCA2 were analyzed. Screening for large rearrangements in both genes was performed by MLPA.


Of 523 index patients, 121 (23.1%) were found to carry a pathogenic or likely pathogenic (class 4/5) mutation. A variant of unknown significance (VUS) was detected in 73/523 patients (13.9%). Two mutations p.Gln1756Profs*74 and p.Cys61Gly comprised 42.3% (n = 33/78) of all detected pathogenic mutations in BRCA1. Most of the other mutations were unique mutations. The most frequently detected mutation in BRCA2 was p.Val1283Lys (13.9%; n = 6/43). Altogether, 101 different neutral genetic variants were counted in BRCA1 (n = 35) and in BRCA2 (n = 66).


The two most frequently detected mutations are founder mutations in Poland and Czech Republic. More similarities seem to be shared with our direct neighbor countries compared to other European countries. For comparison of the extended genotype, a shared database is needed.

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This work would not have been possible without the inspiration, concept and continued effort of Rita Schmutzler and Alfons Meindl and all collaborators of GC-HBOC. We thank the UCV-task force of GC-HBOC for classification of the genetic variants. Special thanks go to Wolfgang Distler for persistent support and encouragement. We thank the German Cancer Aid for supporting of GC-HBOC with Grant No. 110837.

Authors contributions

KK: conception of the work, acquisition, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, final approval of the version to be published. CM: acquisition and interpretation of data, critical revision of the manuscript for important intellectual content, final approval of the version to be published. CES: analysis and interpretation of data, critical revision of the manuscript for important intellectual content, final approval of publication. DK: analysis and interpretation of the data, final approval of publication. NA, PW, AR: interpretation of data, critical revision of the manuscript for important intellectual content, final approval of publication. All other authors: acquisition of data, critical revision of the manuscript for important intellectual content, final approval of publication.

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Correspondence to Karin Kast.

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The authors declare that they have no conflict of interest.


German Cancer Aid Grant No 110837 for GC-HBOC.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (No. EK 162072007) and with the 1064 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

Additional information

C. Meisel and C. E. Sadowski contributed equally to this work.

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Meisel, C., Sadowski, C.E., Kohlstedt, D. et al. Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study. Arch Gynecol Obstet 295, 1227–1238 (2017). https://doi.org/10.1007/s00404-017-4330-z

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  • Mutational spectrum
  • BRCA1
  • BRCA2
  • Germany
  • Hereditary breast cancer