Stepwise Vairant Classification and Interpretation

Copyrighted Figure, displaying here for educational purpose only. See reference below.
Reference: Horak P, et al. Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of ClinGen, CGC, and VICC. Genetics in Medicine 2022;24(5):986-998. (PMID: 35101336)

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Click a link to visit the public database site

Is this variant oncogenic? (Websites I frequently use)

Classification of Variants Based on Oncogenicity calculator Calculator js-html written by Dr. Thomas Schneider, Emory Pathology

Gnomad: Population database (not always germline)

The gnomad database is not user-friendly. You will need to figure out the specific format (see the Examples on the webpage) to perform a search.

Cancer Hotspot: Somatic mutations associated with cancer

Genome Nexus: Integrative Analysis of Cancer Genomics

Including links to OncoKB, ClinVar, gnomAD, dbSNP, and some Functional predictions

Franklin: Clinical Database (QIAGEN)

GeneBe: Genetic Variant Information Portal (default is hg38)

AlphaMissense: Predicting the pathogenicity of missense variants (search by gene name, every amino acid will be listed)

How often do we see this variant in malignancies?
How often do we see this variant in the tested tumor type?

Unfortunately, a few well known public databases have gone offline or requires registration.

TCGA (The Cancer Genome Atlas): Harmonized Cancer Datasets

cBioPortal Public Site

AACR GENIE Public Database: cBioPortal Genie

Genie is a large international consortium, which has collected genomic data from multiple institutions.
This is currently the go to database I use to search for variant frequency in specific tumor types. However, the collection of hematolymphoid malignancies is still limited.

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Evidence-based variant categorization (AMP Tiering System)

Copyrighted Figure, displaying here for educational purpose only. See reference below.
Reference: Li, M. et al. Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn. 2017;19(1):4-23. PMID: 27993330

OncoKB: MSK's Precision Oncology Knowledge Base

CKBBoost: The Clinical Knowledgebase, Powered by The Jackson Laboratory Limited to 50 core genes for free search

CIVIC: Clinical Interpretation of Variants in Cancer Difficult to navigate