Tier models
PCGR performs variant classification, meaning that variants are organized and prioritized according to clinical impact. Currently, PCGR implements its tier classsification framework along the proposed ACMG guidelines, as detailed below.
pcgr_acmg
This tier model attempts to adopt concensus recommendations by ACMG, as outlined in Li et al., 2017:
-
Tier 1: Variants of strong clinical significance -
constitutes variants linked to predictive, prognostic, or diagnostic
biomarkers in the CIViC
database and the Cancer
Biomarkers Database that are
- A: found within the same tumor type/class as specified by the user, AND
- B: of strong clinical evidence (i.e. part of guidelines, validated or discovered in late clinical trials)
-
Tier 2: Variants of potential clinical significance -
constitutes other variants linked to predictive, prognostic, or
diagnostic biomarkers in the CIViC database and the Cancer
Biomarkers Database that are either
- A: of strong clinical evidence in other tumor types/classes than the one specified by the user, OR
- B: of weak clinical evidence (early trials, case reports etc.) in the same tumor type/class as specified by the user
- Tier 3: Variants of uncertain clinical significance - includes other coding variants found in oncogenes or tumor suppressor genes
- Tier 4 - includes other coding variants
For copy number aberrations, aberrations linked to Tier 1 & 2 are displayed, within following sections in the HTML report:
- Copy number aberrations as biomarkers: Aberrations of strong clinical significance (Tier 1)
- Copy number aberrations as biomarkers: Aberrations of potential clinical significance (Tier 2)