loading page

A decade of RAD51C/D: Germline pathogenic variants and their phenotypic landscape
  • +8
  • Jacopo Boni,
  • Aida Idani,
  • Carla Roca,
  • Lídia Feliubadaló,
  • Eva Tomiak,
  • Evan Weber,
  • William Foulkes,
  • Alex Orthwein,
  • Zaki el Haffaf,
  • Conxi Lazaro,
  • Barbara Rivera
Jacopo Boni

Corresponding Author:[email protected]

Author Profile
Aida Idani
Author Profile
Carla Roca
Author Profile
Lídia Feliubadaló
Catalan Institute of Oncology
Author Profile
Eva Tomiak
Children's Hospital of Eastern Ontario
Author Profile
Evan Weber
McGill University Health Centre
Author Profile
William Foulkes
McGill University Health Centre
Author Profile
Alex Orthwein
McGill University
Author Profile
Zaki el Haffaf
Centre Hospitalier de l'Universite de Montreal
Author Profile
Conxi Lazaro
Author Profile
Barbara Rivera
Author Profile


Defects in DNA repair genes have been extensively associated to cancer susceptibility. Germline pathogenic variants (GPV) in genes involved in homologous recombination repair pathway predispose to cancers arising mainly in breast and ovary, but also other tissues. The RAD51 paralogs RAD51C and RAD51D were included in this group 10 years ago, when germline variants were associated to non-BRCA1/2 familial ovarian cancer. However, whether GPVs in these genes are associated with other cancers remains unknown. Here, we have reviewed the landscape of RAD51C and RAD51D germline variants in cancer reported in the literature during the last decade, curating a total of 341 variants and the phenotypes found in families with RAD51C/D variant carriers. A comprehensive catalogue has been generated pinpointing to the existence of recurrent variants in both genes. Investigation of pedigrees found fourteen other cancer types reported more than five times in families with carriers of RAD51C/D pathogenic variants. Among those, colorectal (3.72% and 4.43%) (RAD51C/D respectively), pancreatic (1.19% and 0.86%), lung (1.27% and 2.58%), prostate (1.56% and 1.48%), and leukemia (1.56% and 1.11%) cancer were the most prevalent types. This work highlights how both genes might confer susceptibility to a broader spectrum of cancer types than ovary and breast.
25 Aug 2021Submitted to Human Mutation
26 Aug 2021Submission Checks Completed
26 Aug 2021Assigned to Editor
06 Sep 2021Reviewer(s) Assigned
05 Oct 2021Review(s) Completed, Editorial Evaluation Pending
15 Oct 2021Editorial Decision: Revise Major
30 Nov 20211st Revision Received
01 Dec 2021Submission Checks Completed
01 Dec 2021Assigned to Editor
02 Dec 2021Review(s) Completed, Editorial Evaluation Pending
07 Dec 2021Editorial Decision: Revise Minor
08 Dec 20212nd Revision Received
09 Dec 2021Submission Checks Completed
09 Dec 2021Assigned to Editor
09 Dec 2021Review(s) Completed, Editorial Evaluation Pending
15 Dec 2021Editorial Decision: Accept