A direct comparison of dnLGD and dnMIS variant counts for each gene in the combined NDD cohort (n = 11,409 genes) identifies 12 genes (ARID1B, ADNP, KMT2A, DYRK1A, CTNNB1, SETD5, GATAD2B, WAC, ASXL1, ASXL3, ARID2, and PPM1D) significantly enriched for dnLGD when compared to dnMIS variants (two-sided Fisher’s exact test, FDR 5%). Here, SETD5 is linked to Neurodevelopmental delay.