CHD8 and Neurodevelopmental delay: Heterozygotes for rare LoFs in three (NAV3, SCAF1 and HNRNPUL2) of the four new genes with substantial contribution from rare inherited variants have similar IQ distribution as the overall SPARK cohort (Fig. 6a), which is substantially higher than heterozygotes with rare LoFs in well-established, highly penetrant genes that contribute to ASD primarily through DNVs (‘DN genes’) such as CHD8, SHANK3 and SCN2A. In fact, both novel and established genes with significant contribution from rare inherited LoFs are less associated with intellectual disability than NDD genes (Fig. 6b).