EDT2. Biallelic Loss of function and damaging functional variants.

Rare (MAF < 5%) biallelic loss-of-function and damaging functional variants in uninherited diplotypes and probands. ‘Likely dominant probands’ refers to probands with a reported de novo mutation or affected parents, and ‘other probands’ to all remaining probands. ‘DDG2P Biallelic’ refers to confirmed and probable DDG2P genes with a biallelic mode of inheritance. See Supplemental methods for details of variant processing.

Biallelic Variant Types	Untransmitted Diplotypes (n=1080)	Likely Dominant Probands (n=270)	Other Probands (n=810)
LoF/LoF (Genome-wide)	110	17	86
LoF/Dam (Genome-wide)	87	21	71
Dam/Dam (Genome-wide)	312	90	264
LoF/LoF (DDG2P Biallelic)	1	1	3
LoF/Dam (DDG2P Biallelic)	2	0	6
Dam/Dam (DDG2P Biallelic)	26	7	25