Table 2. Novel genes with compelling evidence for a role in DD.

Evidence	Gene	de novos DDD (Missense, LoF)	de novos Meta (Missense, LoF)	P Value	Test	Mutation Clustering	Predicted Haploinsufficiency
De novo enrichment	COL4A3BP	3 (3,0)	5 (5,0)	4.10E-12	Meta	Yes	14.7%
	PPP2R5D	4 (4,0)	5 (5,0)	6.01E-12	DDD	Yes	19.7%
	ADNP	4 (0,4)	5 (0,5)	4.59E-11	Meta	No	9.8%
	POGZ	2 (0,2)	5 (0,5)	4.31E-10	Meta	No	30.0%
	PPP2R1A	3 (3,0)	3 (3,0)	2.03E-08	DDD	Yes	23.5%
	DDX3X	4 (3,1)	5 (3,2)	2.26E-07	DDD	No	12.7%
	CHAMP1	2 (0,2)	3 (0,3)	4.58E-07	Meta	No	52.9%
	BCL11A	3 (3,0)	4 (3,1)	1.03E-06	DDD	Yes	0.6%
	PURA	3 (1,2)	3 (1,2)	1.14E-06	DDD	No	9.4%
De novo enrichment + additional evidence	DNM1	3 (3,0)	5 (5,0)	1.43E-06	Meta	No	13.5%
	TRIO	2 (2,0)	7 (7,0)	5.16E-06	Meta	Yes	25.7%
	PCGF2	2 (2,0)	2 (2,0)	1.08E-05	DDD	Yes	37.7%

The table summarises the 12 genes with compelling evidence to be novel DD genes. The number of unrelated patients with independent functional or LoF mutations in the DDD cohort or the wider meta-analysis dataset including DDD patients is listed. The p value reported is the minimum p value from the testing of the DDD dataset and the meta-analysis dataset. The dataset that gave this minimal p value is also reported. Mutations are considered to be clustered if the p value of clustering of functional SNVs is less than 0.01. Predicted haploinsufficiency is reported as a percentile of all genes in the genome, with ~0% being highlight likely to be haploinsufficient and 100% very unlikely to be haploinsufficient, based on the prediction score described in Huang et al ²⁶ updated to enable predictions for a higher fraction of genes in the genome. During submission, a paper was published online describing a novel DD caused by mutations in ADNP ²⁷.