Table 2.

Burden testing in IGD vs. gnomAD cohort

Chr	bp	Ref	Alt	Annotation	Location	Daignosis	Gender	Additional features	Other genes	Ethnicity	GnomAD MAF based in subpopulation ethnicity
12	97 858 842	A	G		Exon 1	KS	Male		KLB c.820A > G p.I274V het; FGFR1 c.1097C > T p.P366L het	Asian	None
12	97 858 843	T	C		Exon 1	nIHH	Male			Caucasian	None
12	97 886 308	G	C		Exon 3	KS	Male	External ear defect		Not assessed	0.003094 (East Asian)
						KS	Female	Eye defects, speech impairement & cerebellar ataxia		Asian	None
12	97 887 656	T	A		Exon 5	KS	Male	Synkinesia	KAL1 c.1759G > T p.V587L hem	Caucasian	None
12	97 887 663	G	A	n.256-6G > A	Exon 5	nIHH	Male	No		Caucasian	0.0002665 (non-Finish Europeans); 0.0002862 (Finish Europeans)
12	97 887 706	T	A		Exon 5	niHH	Male	No		Caucasian	None
12	97 887 763	G	A		Exon 5	KS	Male	No		Not assessed	0.00006666 (non-Finish European)
12	97 888 490	C	T		Exon 6	KS	Male	No		African american	0.003212
12	97 888 657	A	G	n.1521A > G	Exon 6						0.002749
12	97 927 340	T	C		Exon 9						0.001375
12	97 889 772	C	A		Exon 7	KS	Male	Flat feet, kyphosis, and hypermobility		Caucasian	0.0002667
12	97 926 773	G	T		Exon 9	nIHH	Male	No		Caucasian	None
						nIHH	Male	Flat feet and eye defects	GLCE c.427G > A p.V143M het; POLR3B c.1-1C > T het; CHD7 c.7315G > A p.E2439K het; PNPLA6 c.1484C > T p.P495L het	Caucasian
12	97 926 848	C	T		Exon 9	KS	Male	Deviated septum and high arched palate	PROKR2 c.254G > A p.R85H het	Caucasian	0.0006676 (non-Finish European); 0.0002862 (Finish)
12	97 926 848	C	G		Exon 9	KS	Male	Clinodactyly and neurologic defects		Asian	None
12	97 962 885	G	A		Exon 9	nIHH	Female	CL/CP	IL17RD c.1697C > T p.P566L het	African American	None
						nIHH	Male	No		Not assessed
						KS	Male	Flat feet and pectus excavatum	OTUD4 c.755T > C p.V252A het	Asian
						nIHH	Male	No	CHD7 c.2831G > A p.R944H het; PROKR2 c.991G > A p.V331M het; FGFR1 c.289G > A p.G97S het	Asian
						nIHH	Male	Ataxia		Not assessed
						KS	Male	Synkinesia	KLB c.1825A > G p.T609A het	Asian
						nIHH	Female	No	PROK2 c.218G > A p.R73H het	Asian
						nIHH	Male	Crowded teeth and protruding ears	CHD7 c.120A > C p.Q40H het; CHD7 c.4565A > T p.D1522V het; PROKR2 c.949G > C p.V317L het	Caucasian
12	97 927 223	C	T		Exon 9	KS	Male	Excessive joint mobility, high arched palate, synkinesia	KAL1 c.1056_1060delGGATG p.T352TfsX2 hem; CHD7 c.8416C > G p.L2806V het	Not assessed	0.0003339 (non-Finish European); 0.0002862 (Finish Europeans); 0.001196 (Latino); 0.001018 (other)
						nIHH	Male	No		Caucasian
12	97 927 489–97 927 490	GC	G		Exon 9	nIHH	Female	No	TACR3 c.623G > A p.W208X het	Caucasian	0.001671 (non-Finish Europeans); 0.0002864 (Finish Europeans)
						KS	Male	Curved spine, foreshortened arm/leg, and bone deformities	CHD7 c.5051-4C > T het; LEPR c.2246T > C p.L749S het; FGFR1 c.745 + 7G > A het; FGFR1 c.1809C > A p.C603X het	Caucasian
						nIHH	Male	No	GNRHR c.892_893insA p.N298KfsX22 hom; KISS1R c.998C > T p.A333V het	Caucasian
						nIHH	Male	No	IL17RD c.2012C > T p.S671L het; POLR3B c.543A > C p.Q181H het;	Caucasian
						nIHH	Male	No		Caucasian
						nIHH	Male	No		Caucasian
						nIHH	Male	No	CHD7 c.2819C > T p.P940L het; also WES data not back	Caucasian

Table shows prevalence of rare variation (MAF < 1%) and very rare variation (MAF < 0.1%) in the IGD cohort and the reference-control database of the gnomAD. The statistical differences were calculated between cohort of similar genetic background. Abbreviations: MAF: minor allele frequency; N/A: not available.