The performances of variant prioritization approaches were compared. All disease-associated genes were ranked using the respective variant prioritization method. Subsequently, the proportion of cases detected with the correct disease-associated gene (sensitivity) was shown as a function of the number of disease-associated genes considered, beginning at the top score. The following four approaches for variant prioritization were tested in solved cases from the PEDIA cohort ( n = 94): (1) only a molecular pathogenicity score (CADD 68 ) with top-10 accuracy of 48%; (2) feature-based score (CADA 69 ) in addition to CADD with top-10 accuracy of 68%; and (3 and 4) a gestalt score from facial image analysis (GestaltMatcher 40 ) alone or in addition to both CADD and CADA referred to as PEDIA score 41 with top-10 accuracy of 82%. Note that the bold lines indicate the observed top- k accuracy and bootstrapped 95% CIs are indicated by the lighter shading around the lines. MRI, magnetic resonance imaging; abn., abnormality; con., congenital; dysf., dysfunction; psych., psychiatric; sym., symptoms; sec, secondary.
