Table 2.

Variants in 37 DSD-related genes identified in 35 patients with 46,XY DSD.

ID	Sex#	DSD category	Clinical diagnosis	DSD gene	Inheritance	GnomAD frequency	DNA change	Protein change	SIFT	MT	ACGM classification
4	M	DGD	TRS	POR	AR	0.25%	c.683C>T	p.Pro228Leu	D	D	VUS
9	F	DGD	CGD	AR	XL		(CAG)28				VUS
11	M	DAS	5αRD	HOXA13	AD		c.539C>T	p.Pro180Leu	D	D	Likely pathogenic
				ARX	XL	0.00%	c.1315_1320dupGCCGCC	p.Ala439delinsGlyArgPro			VUS
12	M	DAS	5αRD	AMH	AR	0.01%	c.1013G>A	p.Arg338His	D	T	VUS
				AKR1C4	AR	0.00%	c.467A>C	p.Asp156Ala	D	D	VUS
13	F	DAS	DAS	HSD17B3	AR	0.01%	c.729_735delGATAACC	p.Ile244Argfs*11			Pathogenic
				HSD17B3	AR	0.03%	c.277+4A>T				Pathogenic
				CYP17A1	AR		c.666+5G>A				VUS
14	M	DAA	NSDUM	WT1	AD		c.605T>G	p.Leu202Arg	D	U	Likely pathogenic
15	M	DAA	NSDUM	AR	XL		c.2199C>A	p.Asp733Glu	D	D	Pathogenic
				SOX9	AD		c.847A>G	p.Ile283Val	D	D	VUS
				POR	AR	0.01%	c.1586C>T	p.Thr529Met	D	D	VUS
16	M	DAA	NSDUM	HSD17B3	AR	0.01%	c.729_735delGATAACC	p.Ile244Argfs*11			VUS
18	M	DAA	NSDUM	CBX2	AR		c.460delT	p.Cys154Alafs*62			VUS
				AR	XL		(CAG)28				VUS
20	F	DAA	CAIS	AR	XL		c.1715A>G	p.Tyr572Cys	D	D	Pathogenic
21	F	DAA	CAIS	AR	XL		c.2086G>A	p.Asp696Asn	D	D	Pathogenic
22	F	DAA	CAIS	AR	XL		c.2546dupA	p.Asn849Lysfs*32			Pathogenic
23	F	DAA	CAIS	AR	XL		c.2222C>A	p.Ser741Tyr	D	D	Pathogenic
				POR	AR	0.03%	c.571G>C	p.Val191Leu	T	D	VUS
24	F	DAA	CAIS	AR	XL		c.1822C>T	p.Arg608*	U	D	Pathogenic
25	F	DAA	CAIS	AR	XL		c.2222C>T	p.Ser741Phe	D	D	Pathogenic
26	F	DAA	CAIS	AR	XL		c.2086G>A	p.Asp696Asn	D	D	Pathogenic
				DHCR7	AR	0.01%	c.89G>C	p.Gly30Ala	D	D	VUS
27	F	DAA	PAIS	NR5A1	AR;AD		c.274C>T	p.Arg92Trp	D	D	Pathogenic
32	M	sDSD	sDSD	STAR	AR		c.65-2A>T				VUS
33	M	sDSD	sDSD	AR	XL		(CAG)29				VUS
34	M	sDSD	sDSD	AR	XL		(CAG)29				VUS
				DMRT1	AD	0.26%	c.671A>G	p.Asn224Ser	D	D	VUS

All variants listed are heterozygous, with the exception of changes in AR and ARX, which are hemizygous as these genes are on the X chromosome. The number of CAG repeats leading to the expansion of the polyglutamine tract in the AR gene is specified with the index number.

^#Sex of rearing.

5αRD, 5α-reductase deficiency; ACMG, American College of Medical Genetics and Genomics; AD, autosomal dominant; AR, autosomal recessive; CAIS, complete androgen insensitivity syndrome; CGD, complete gonadal dysgenesis; D, deleterious; DAA, disorder of androgen action; DAS, disorder of androgen synthesis; DGD, disorder of gonadal development; DSD, disorder of sex development; F, female; GnomAD, Genome Aggregation Database; M, male; MT, MutationTaster; NSDUM, nonspecific disorder of undermasculinization; PAIS, partial androgen insensitivity syndrome; sDSD, syndromic disorder of sex development; SIFT, Sorting Intolerant From Tolerant; T; tolerated; TRS, testicular regression syndrome; U, unknown; VUS, variant of uncertain significance; XL, X-linked.