Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC)

Peter Horak, Malachi Griffith, Arpad M. Danos, Beth A. Pitel, Subha Madhavan, Xuelu Liu, Cynthia Chow, Heather Williams, Leigh Carmody, Lisa Barrow-Laing, Damian Rieke, Simon Kreutzfeldt, Albrecht Stenzinger, David Tamborero, Manuela Benary, Padma Sheila Rajagopal, Cristiane M. Ida, Harry Lesmana, Laveniya Satgunaseelan, Jason D. MerkerMichael Y. Tolstorukov, Paulo Vidal Campregher, Jeremy L. Warner, Shruti Rao, Maya Natesan, Haolin Shen, Jeffrey Venstrom, Somak Roy, Kayoko Tao, Rashmi Kanagal-Shamanna, Xinjie Xu, Deborah I. Ritter, Kym Pagel, Kilannin Krysiak, Adrian Dubuc, Yassmine M. Akkari, Xuan Shirley Li, Jennifer Lee, Ian King, Gordana Raca, Alex H. Wagner, Marylin M. Li, Sharon E. Plon, Shashikant Kulkarni, Obi L. Griffith, Debyani Chakravarty, Dmitriy Sonkin

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Purpose: Several professional societies have published guidelines for the clinical interpretation of somatic variants, which specifically address diagnostic, prognostic, and therapeutic implications. Although these guidelines for the clinical interpretation of variants include data types that may be used to determine the oncogenicity of a variant (eg, population frequency, functional, and in silico data or somatic frequency), they do not provide a direct, systematic, and comprehensive set of standards and rules to classify the oncogenicity of a somatic variant. This insufficient guidance leads to inconsistent classification of rare somatic variants in cancer, generates variability in their clinical interpretation, and, importantly, affects patient care. Therefore, it is essential to address this unmet need. Methods: Clinical Genome Resource (ClinGen) Somatic Cancer Clinical Domain Working Group and ClinGen Germline/Somatic Variant Subcommittee, the Cancer Genomics Consortium, and the Variant Interpretation for Cancer Consortium used a consensus approach to develop a standard operating procedure (SOP) for the classification of oncogenicity of somatic variants. Results: This comprehensive SOP has been developed to improve consistency in somatic variant classification and has been validated on 94 somatic variants in 10 common cancer-related genes. Conclusion: The comprehensive SOP is now available for classification of oncogenicity of somatic variants.

Original languageEnglish
Pages (from-to)986-998
Number of pages13
JournalGenetics in Medicine
Volume24
Issue number5
DOIs
StatePublished - May 2022

Keywords

  • Cancer genetic testing
  • Oncogenicity
  • Pathogenicity
  • Somatic variant
  • Variant classification

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