A set of evolutionarily highly constrained genes were also analysed. The set of highly constrained genes was defined using a posterior probability of being loss-of-function intolerant (pLI) based on the observed and expected counts of protein-truncating variants (PTV) within each gene in a large study of over 60,000 exomes from the Exome Aggregation Consortium (ExAC)91. Genes with pLI ≥0.9 were selected as the set of highly constrained genes (2932 genes).
