At OncoDNA it has been consensually chosen to follow ACMG-AMP guidelines to classify actionable variants by biological and therapeutical impacts.
Biological classes
There is a general consensus to use these 5 biological classes:
- Pathogenic
- Probably (likely) pathogenic
- VUS
- Probably (likely) benign
- Benign
This classification is based on the ACMG and AMP Standards and Guidelines publication of Richards et al. Genet Med 2015, even though these guidelines are meant for germline variants. Read also https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544753/
Therapeutical classes
TIER I:
Level A:
1. Biomarkers that predict response or resistance to FDA-approved therapies for a specific type of tumor
2. Biomarkers included in professional guidelines that predict response or resistance to therapies for a specific type of tumor
Level B:
Biomarkers that predict response or resistance to therapies for a specific type of tumor based on well-powered studies with consensus from experts in the field
TIER II:
Level C:
1. Biomarkers that predict response or resistance to therapies approved by the FDA or professional societies for a different type of tumor
2. Biomarkers that serve as inclusion criteria for clinical trials
Level D:
Biomarkers that show plausible therapeutic significance based on preclinical studies
TIER III:
Variants of uncertain (or unknown) significance (VUS)
TIER IV:
Likely Benign / Benign
