Reduced penetrance of pathogenic ACMG variants in a deeply phenotyped cohort study and evaluation of ClinVar classification over time.

Jeroen G J van RooijPascal ArpLinda BroerJoost VerlouwFrank van RooijRobert KraaijAndré UitterlindenAnnemieke J M H Verkerk

Published in: Genetics in medicine : official journal of the American College of Medical Genetics (2020)

We show that the definition of "known pathogenic" is often unclear and should be approached carefully. Additionally variants marked as known pathogenic do not always have clinical impact on their carriers. Definition and classification of true (individual) expected pathogenic impact should be defined carefully.

Keyphrases

machine learning
deep learning
copy number
gene expression
genome wide