Table 2 Step B: clinical grading.
From: Stepwise ABC system for classification of any type of genetic variant
Clinical classes | Score | Description | |
|---|---|---|---|
cVUS | Variant of unknown clinical significance—a clinical VUS | 0 | Variant of unknown clinical significance, e.g., a variant in a gene that is unlikely to be linked to the patient’s phenotype. |
Right type of gene | Variant of potential interest (VOI) | 1 | “The right type of gene” because the gene fits the phenotype: (1) dominant variant that could be pathogenic (2) single hypomorphic variant that could be linked to a recessive cause |
Risk factor | Known or assumed risk factor variant | 2 | (1) Low penetrance dominant variant (2) Dominant variant with good clinical support of a pathogenic role (3) Single pathogenic variant in a recessive gene that fits the phenotype |
Pathogenic | Pathogenic variant | 3 | Pathogenic variant |
Pathogenic | Moderate penetrance pathogenic variant | 4 | Dominant pathogenic variant of moderate (20–40%) penetrance |
Pathogenic | High penetrance pathogenic variant | 5 | Dominant pathogenic variant of high (>40%) penetrance |
