OncoKB is a Precision Oncology Knowledgebase that contains information about the biological effects and treatment implications of specific cancer genes and their somatic alterations. OncoKB is developed and maintained by the Knowledge Systems group in the Marie Josée and Henry R. Kravis Center for Molecular Oncology at the Memorial Sloan Kettering Cancer Center (MSK). In OncoKB, genes are classified as either oncogenes or tumor suppressors based on the curated evidence. Alterations included in OncoKB are genetic changes that arise as a result of DNA-level variants in cancer: non-synonymous mutations, translocations, rearrangements / fusions, copy number amplifications and deletions. This document uses “Alterations”, “Mutations” and “Variants” interchangeably. All alterations in OncoKB are classified according to 1) their oncogenic effect and 2) their biological effect, based on the curated evidence (discussed in Chapter 2). The oncogenic effect of an alteration is an evidence-based assertion that classifies whether the mutation is oncogenic, likely oncogenic, neutral or inconclusive. The biological effect of an alteration is an evidence-based assertion that classifies whether the mutation is gain-of-function, loss-of-function, neutral or inconclusive. If a cancer alteration in OncoKB is associated with clinical implications, these implications are also curated in OncoKB (discussed in Chapter 2). Alterations with clinical implications are further assigned a Therapeutic (Chakravarty et al. 2017), Diagnostic and/or Prognostic level of evidence. Each Level of Evidence assignment in OncoKB defines the strength of the evidence that supports the alteration as being a diagnostic, prognostic or therapeutic biomarker.