Table 2.

Pathogenic variants detected by WES and their interpretation by some of the used bioinformatic tools.

Patient	Gene	Transcript ID	Nucleotide Variant	Protein Variant	dbSNP	Inheri Tance	Frequency		ACMG Classification	Prediction Tools
							gnomAD Exomes	500 Greek Exomes		SIFT	PolyPhen2	Mutation Taster	CADD	GERP
1	BMP4	NM_001202.4	c.124G > C	p.[Ala42Pro;=]	rs140920120	M	0.000283	HTZ:0.002	VUS	B	LP	B	22.6	5.19
								HMZ: 0	(BP4, PS3)
	GNRH1	NM_000825.3	c.217C > T	p.[Arg73Ter;=]	rs375970738	P	0.00000805	0	LP	-	-	-	14.98	4.91
									(PVS1, PM2)
	SRA1	NM_001035235.4	c.94C > G	p.[Gln32Glu;=]	rs35610885	M	0.00715	HTZ: 0.008	VUS	P	LP	DC	27.6	5.01
								HMZ: 0	(BP4, PP5)
2	SOX9	NM_000346.4	c.283G > A	p.[Val95Ile;=]	Novel	M	NA	0	VUS	B	LP	DC	23.3	4.24
									(PM2, BP4)
	HS6ST1	NM_004807.3	c.917G > A	p.[Arg306Gln;=]	rs201307896	M	0.000706	0	P	B	LP	DC	29.9	4.78
									(PS3, PM2, PM5, PP5, PP3)
	IL17RD	NM_017563.5	c.1696C > T	p.[Pro566Ser;=]	rs61742267	M	0.0144	HTZ: 0.028	VUS	B	LP	DC	22.6	5.64
								HMZ: 0	(PM5, BP4)

Abbreviations: dbSNP = database Single Nucleotide Polymorphism, gnomAD = Genome Aggregation Database, ACMG = American College of Medical Genetics, SIFT = Sorting Intolerant From Tolerant, Polyphen2 = Polymorphism Phenotyping v2, CADD = Combined Annotation-Dependent Depletion, GERP = Genomic Evolutionary Rate Profiling, M = Maternal, P = Paternal, NA: not annotated, VUS = Variant of Uncertain Significance, B:Benign, P = Pathogenic, LP = Likely Pathogenic, DC = Disease Causing, PD = Probably Damaging, HTZ = Heterozygous, HMZ = Homozygous.