92. The ClinGen Somatic CDWG supports somatic variant curation and interpretation through structured guidance and procedures

Aly Abdelkareem

Jason Saliba

Dr. Jason Saliba is a Senior Scientist in the Griffith laboratory at the Washington University School of Medicine with over 10 years of experience in cancer research. Dr. Saliba’s research is focused on the development and improvement of protocols, classification guidelines, and training methods related to the curation and interpretation of clinically significant information advancing precision medicine in cancer. He was the first full-time editor of the Clinical Interpretation of Variants in Cancer (CIViC) knowledgebase, which is an open access, open source, community-driven web resource for the curation of somatic variant evidence. Dr. Saliba founded and chairs the Pediatric Cancer Curation Advancement Subcommittee (PCCAS), which is a collaboration between CIViC, the ClinGen Pediatric Cancer Taskforce, and Disease Ontology, with the goal of enhancing pediatric cancer curation and the public dissemination of high-quality childhood focused interpretations. He serves as the Coordinator of the ClinGen Somatic Cancer Clinical Domain Working group, its Taskforces, and Somatic Cancer Variant Curation Expert Panels.


Jason Salibaa, Arpad Danosa, Ian Kingb, Shamini Selvarajahb, Xinjie Xuc, Rashmi Kanagal-Shamannad, Laveniya Satgunaseelane, David M. Meredithf, Kilannin Krysiaka, Mark G. Evansg, Charles G. Mullighanh, Yassmine Akkarii, Gordana Racaj, Angshumoy Royk, Ramaswamy Govindana, Obi L Griffitha, Malachi Griffitha, on behalf of the ClinGen Somatic CDWG

aWashington University School of Medicine, St. Louis, MO, United States; bPrincess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada; cMayo Clinic, Rochester, MN, United States; dThe University of Texas MD Anderson Cancer Center, Houston, TX, United States; eRoyal Prince Alfred Hospital and the University of Sydney, Sydney, NSW, Australia; fDana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States; gCaris Life Sciences, Phoenix, AZ, United States; hSt. Jude Children’s Research Hospital, Memphis, TN, United States; iNationwide Children’s Hospital, Columbus, OH, United States; jChildren’s Hospital Los Angeles, Los Angeles, CA, United States; kBaylor College of Medicine, Houston, TX, United States; ClinGen Somatic CDWG, St. Louis, MO, United States

Interpretation of the clinical significance of somatic variants in cancer remains a major challenge in cancer diagnosis, prognosis, and treatment decisions. The Clinical Genome Resource (ClinGen) Somatic Cancer Clinical Domain Working Group (CDWG) supports data curation and the development of guidelines to standardize clinical significance interpretation of somatic alterations in cancer. The Somatic CDWG actively recruits new members to subspecialty-focused Taskforces (Pediatric, Hematologic, and Solid Tumor) and provides organization and curation training. Taskforces’ targeted curation projects, which often focus on challenging areas of clinical interpretation, serve as building blocks for the formation of Somatic Cancer Variant Curation Expert Panels (SC-VCEPs).

To assist SC-VCEPs through the 4-step ClinGen approval process, the Somatic CDWG has created templates for initial application, modified classification rule submission, and selection of pilot variants. These standards have led to the development of the first NTRK fusion specific oncogenicity classification guidelines and the modification of the ClinGen/CGC/VICC Oncogenicity guidelines [PMID:35101336] for FGFR3, FLT3, and Histone H3 variants. To ensure sustained curation and expert-reviewed clinical interpretations, the Somatic CDWG deploys a paired team approach of experts plus curators to evaluate evidence and create high-quality, clinically-significant somatic cancer variant assertions. Through extensive collaboration with CIViC, SC-VCEPs’ high-level clinical and oncogenic assertions are publicly available and inclusive of any applicable SC-VCEP specific classification codes.

ClinGen Somatic groups have generated 738 CIViC Evidence Items and 34 Assertions of clinical significance from over 400 published papers. Our Taskforces and SC-VCEPs foster collaboration, innovation, and most importantly, advancement of precision medicine.