Title

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).

Document Type

Article

Publication Date

5-1-2022

Publication Title

Genetics in medicine : official journal of the American College of Medical Genetics

Keywords

JGM, Genetic Testing, Genetic Variation, Genome, Human, Genomics, Humans, Neoplasms, Virulence

JAX Source

Genet Med 2022 May; 24(5):986-998

Volume

24

Issue

5

First Page

986

Last Page

998

ISSN

1530-0366

PMID

35101336

DOI

https://doi.org/10.1016/j.gim.2022.01.001

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.

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