Fig. 7.

Enrichment of damaging variants with level of mosaicism. The exome sequencing variant allele fraction (VAF) for candidate DNMs is plotted against the number of damaging (loss-of-function and functional) variants divided by the number of synonymous variants in each of six VAF bins (0.10– < 0.15, 0.15– < 0.20, 0.20– < 0.25, 0.25– < 0.30, 0.30– < 0.35 and >0.35). The number of variants in each VAF bin was further divided into three subgroups of genes, and the significance of the linear regression coefficient versus the null was assessed using a Z-test: genes not currently known to be DD-associated (Not-DDG2P, gray; p = 0.03), genes known to be DD-associated (DDG2P, orange; p = 0.00007), and known monoallelic DD-associated genes with a loss-of-function mechanism (DDG2P-MonoLOF, magenta; p < 0.00001). Gray zones represent 95% confidence intervals. Null values assuming no enrichment (dotted black line) were calculated from published values of expected numbers of variants in each class based on ExAC, adjusted for indels, and summed across all genes