Adoption of a “Pathogenic, Predisposing, Risk and Benign” classification of DNA variants for precision medicine – a step forward
DOI:
https://doi.org/10.69734/h7x6zm57Keywords:
genetic, complex trait genetics, pathogenic variant , risk variant, polygenic risk score, predisposing variant, ACMG, variant of unknown significance, precision medicineAbstract
Precision medicine is often at odds with medical genetics in classifying gene mutations that have high impact on protein expression or function but do not “cause” disease. A new proposal aims to expand the terminology for genetic variants along a spectrum:
(1) pathogenic (retaining Medical Genetics meaning)
(2) predisposing (new term)
(3) risk (as used in PRS)
(4) benign (used in contrast to “pathogenic” but may be “predisposing” in some circumstances and context)
This framework bridges the gap between binary classifications and the nuanced reality of variant effects, paving the way for more accurate risk assessment in clinical practice.
It is time for adoption by geneticists and major professional societies.
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