Table 2 Probands, CHARGE major diagnostic features, gene variants, and pathogenicity evidence

From: Genetic analysis of CHARGE syndrome identifies overlapping molecular biology

Proband	CHARGE major criteria				Gene	Genomic position	cDNA variant	Protein alteration	CADD score	GERP score	Inheritance	Status
	Coloboma	Choanal atresia or cleft palate	Abnormal external, middle, or inner ears	Pathogenic CHD7 variant
502	+	+	+	+	CHD7	chr8: 61,761,664	c.5355G>A	p.Trp1785*	48	5.87	De novo	Known
503	+	+	−	+	CHD7	chr8: 61,655,332	c.1342_1343delAG	p.Arg448Glufs*126	N/A	5.539	De novo	Novel
504	+	+	+	+	CHD7	chr8: 61,754,595	c.4835delA	p.Asn1612Ilefs*28	N/A	3.85	Unknown	Novel
505	+	+	+	+	CHD7	chr8: 61,773,655	c.7802dupA	p.Tyr2601*	N/A	5.73	De novo	Novel^a
506	+	−	+	+	CHD7	chr8: 61,736,406	c.3209delT	p.Val1070Glyfs*2	N/A	5.69	De novo	Novel^a
507	+	+	−	+	CHD7	chr8: 61,742,962	c.3606_3616dupAGAAACTATTA	p.Ile1206Lysfs*9	N/A	5.47	De novo	Novel^a
508	+	+	+	+	CHD7	chr8: 61,757,970	c.5210+2T>C		22.6	5.48	De novo	Novel^b
509	+	−	−	+	CHD7	chr8: 61,714,150	c.2440C>T	p.Gln814*	44	6.17	Inherited	Known
510	+	+	+	+	CHD7	chr8: 61,750,761	c.4480C>T	p.Arg1494*	48	4.42	Unknown	Known
511	+	−	−	+	CHD7	chr8: 61,763,056	c.5409T>G	p.Tyr1803*	49	−1.18	De novo	Novel
512	+	−	+	+	CHD7	chr8: 61,654,916	c.925C>T	p.Gln309*	40	5.56	Unknown	Known
513	+	+	+	+	CHD7	chr8: 61,765,241	c.6079C>T	p.Arg2027*	49	3.64	De novo	Known
514	+	−	+	+	CHD7	chr8: 61,734,662	c.2915A>G	p.Gln972Arg	24.7	5.53	De novo	Novel
515	+	+	+	+	CHD7	chr8: 61,736,402	c.3205C>T	p.Arg1069*	45	5.69	De novo	Known
516	+	+	+	+	CHD7	chr8: 61,735,210	c.3106C>T	p.Arg1036*	45	5.53	De novo	Known
517	+	+	+	−	RERE	chr1: 8,418,276	c.4313_4318dupTCCACC	p.Leu1438_His1439dup	N/A	5.61	De novo	Known
518	+	−	+	−	KMT2D	chr12: 49,431,536	c.9602dupT	p.Ser3202Glufs*13	N/A	−0.809	Unknown	Novel
519	+	+	+	−	KDM6A	chrX: 44,820,553	c.250A>G	p.Ile84Val	17.16	5.66	X-linked recessive	Novel
520	−	+	+	−	EP300	chr22: 41,553,171	c.3262-2A>G		24.4	5.7	De novo	Novel
521	+	−	−	−	PUF60	chr8:144,900,664	c.389G>A	p.Arg130His	25.9	5.18	De novo	Novel

CADD, combined annotation dependent depletion; cDNA, complementary DNA; GERP, genomic evolutionary rate profiling; known, identified in CHD7 database and defined as pathogenic; N/A, not applicable; novel^a, known frameshifts observed at this protein position and defined as pathogenic; novel^b, a splice-site variant is observed one nucleotide away at c.5210+3A>G and defined as pathogenic.
Known or novel status of CHD7 variants were defined according to presence in the CHD7 database at http://molgenis51.gcc.rug.nl on 29 June 2017. Known CHD7 variants were also observed in 1000 Genomes with an association to CHARGE syndrome by the Human Gene Mutation Database or ClinVar.

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Table 2 Probands, CHARGE major diagnostic features, gene variants, and pathogenicity evidence

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