Fig. 1: Clinical relevance of cancer gene variants.
a, Overview of gene mutations (single-nucleotide variants and small indels) reported as biomarkers of cancer diagnosis, prognosis and/or drug response by three publicly available knowledge bases (CIViC (Clinical Interpretation of Variants in Cancer), OncoKB (Oncology Knowledge Base) and CGI (Cancer Genome Interpreter)6,7,8) at the moment of writing. An assertion corresponds to a reported biomarker effect for a given gene variant, in a given cancer type and with a given level of supporting evidence. Assertions supported by weaker or inconclusive evidence (as provided by the knowledge base metadata when appropriate; Methods) are excluded from these results. 1,000g, 1000 Genomes Project; AF, allele frequency. b, Representation of distinct levels of interpretation for cancer gene variants. The functional relevance evaluates the allele-centric effect of the observed variant, whereas context-dependent interpretation factors in additional considerations (such as whether the variant is germline or somatic, co-occurring alterations in the same or other genes and/or the cancer type of the patient’s tumor). Questions that are addressed in each step are exemplified here for a given BRCA1 mutation (HRR, homologous recombination repair; PARPi, poly-ADP ribose polymerase inhibitors).
