TY - JOUR
T1 - Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity)
T2 - Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC)
AU - Horak, Peter
AU - Griffith, Malachi
AU - Danos, Arpad M.
AU - Pitel, Beth A.
AU - Madhavan, Subha
AU - Liu, Xuelu
AU - Chow, Cynthia
AU - Williams, Heather
AU - Carmody, Leigh
AU - Barrow-Laing, Lisa
AU - Rieke, Damian
AU - Kreutzfeldt, Simon
AU - Stenzinger, Albrecht
AU - Tamborero, David
AU - Benary, Manuela
AU - Rajagopal, Padma Sheila
AU - Ida, Cristiane M.
AU - Lesmana, Harry
AU - Satgunaseelan, Laveniya
AU - Merker, Jason D.
AU - Tolstorukov, Michael Y.
AU - Campregher, Paulo Vidal
AU - Warner, Jeremy L.
AU - Rao, Shruti
AU - Natesan, Maya
AU - Shen, Haolin
AU - Venstrom, Jeffrey
AU - Roy, Somak
AU - Tao, Kayoko
AU - Kanagal-Shamanna, Rashmi
AU - Xu, Xinjie
AU - Ritter, Deborah I.
AU - Pagel, Kym
AU - Krysiak, Kilannin
AU - Dubuc, Adrian
AU - Akkari, Yassmine M.
AU - Li, Xuan Shirley
AU - Lee, Jennifer
AU - King, Ian
AU - Raca, Gordana
AU - Wagner, Alex H.
AU - Li, Marylin M.
AU - Plon, Sharon E.
AU - Kulkarni, Shashikant
AU - Griffith, Obi L.
AU - Chakravarty, Debyani
AU - Sonkin, Dmitriy
N1 - Publisher Copyright:
© 2022
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
KW - Cancer genetic testing
KW - Oncogenicity
KW - Pathogenicity
KW - Somatic variant
KW - Variant classification
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U2 - 10.1016/j.gim.2022.01.001
DO - 10.1016/j.gim.2022.01.001
M3 - Article
C2 - 35101336
AN - SCOPUS:85123717727
SN - 1098-3600
VL - 24
SP - 986
EP - 998
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 5
ER -