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Practice Guideline
. 2022 May;24(5):986-998.
doi: 10.1016/j.gim.2022.01.001. Epub 2022 Jan 29.

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  1 , Malachi Griffith  2 , Arpad M Danos  2 , Beth A Pitel  3 , Subha Madhavan  4 , Xuelu Liu  5 , Cynthia Chow  6 , Heather Williams  7 , Leigh Carmody  8 , Lisa Barrow-Laing  9 , Damian Rieke  10 , Simon Kreutzfeldt  11 , Albrecht Stenzinger  12 , David Tamborero  13 , Manuela Benary  10 , Padma Sheila Rajagopal  14 , Cristiane M Ida  3 , Harry Lesmana  15 , Laveniya Satgunaseelan  16 , Jason D Merker  17 , Michael Y Tolstorukov  5 , Paulo Vidal Campregher  18 , Jeremy L Warner  19 , Shruti Rao  4 , Maya Natesan  2 , Haolin Shen  2 , Jeffrey Venstrom  20 , Somak Roy  21 , Kayoko Tao  22 , Rashmi Kanagal-Shamanna  23 , Xinjie Xu  3 , Deborah I Ritter  24 , Kym Pagel  25 , Kilannin Krysiak  2 , Adrian Dubuc  26 , Yassmine M Akkari  27 , Xuan Shirley Li  28 , Jennifer Lee  29 , Ian King  30 , Gordana Raca  31 , Alex H Wagner  32 , Marylin M Li  33 , Sharon E Plon  24 , Shashikant Kulkarni  24 , Obi L Griffith  2 , Debyani Chakravarty  34 , Dmitriy Sonkin  35
Affiliations
Practice Guideline

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 et al. Genet Med. 2022 May.

Erratum in

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.

Keywords: Cancer genetic testing; Oncogenicity; Pathogenicity; Somatic variant; Variant classification.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest L.B.-L. was an employee at QIAGEN Inc at the time of contribution. J.D.M. is a consultant for PierianDx Inc. J.V. is an employee at Foundation Medicine, Inc; Genentech, Inc, and Roche AG and owns stock of Roche AG. X.S.L. is an employee at Congenica Ltd.

Figures

Figure 1.
Figure 1.
Somatic SOP Evidence Framework Overview (not all criteria are listed).
Figure 2.
Figure 2.
Stepwise process of somatic variant classification and interpretation.
See this image and copyright information in PMC

Comment in

References

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