Screening of premature ovarian insufficiency associated genes in Hungarian patients with next generation sequencing

Table 2 Potential susceptibility factors found in 17 POI patients via targeted panel sequencing

Gene	dbSNP ID	Sequence changes		Type	ClinVar	MAF	Pathogenicity						Patients ID	Reference
Gene	dbSNP ID	cDNA	AA	Type	ClinVar	MAF	P/B	CADD	VEST	SIFT	PolyPhen	GERP++	Patients ID	Reference
AIRE	rs72650677	c.1322 C > T	T441M	Missense	VUS	< 0.01	6/21	12	0.73	0.02	0.24	0.63	P08	[22]
DACH2	rs147377892	c.107 C > T	P36L	Missense	-	< 0.01	11/12	21	0.10	0	0.02	4.49	P03	[23]
DACH2	rs148179765	c.1245G > C	E415D	Missense	-	< 0.01	7/16	16	0.08	0.3	0.08	1.81	P14	*
EIF2B4	rs41288827	c.*1C > T	-	Splice site	B	0.01	0/2	4	-	-	-	-3.26	P11, P12, P31, P40	[16]
FMR1	rs139029212	c.818 A > G	K273R	Missense	VUS	< 0.01	7/16	21	0.25	0.49	1	5.78	P10	[24]
GALT	rs2070074	c.940 A > G	N314D	Missense	VUS	0.095	2/19	17	0.77	1	0	5.3	P23, P26, P29, P31, P32, P44, P45, P48	*
HS6ST2	rs181526961	c.146 C > T	S49L	Missense	-	0.01	4/6	24	0.34	0	0.92	3.65	P37, P38, P39	*
NOBOX	rs139083352	c.1849 C > T	H617Y	Missense	-	< 0.01	3/20	3	0.18	0.18	0.01	0.48	P26	*
NOBOX	rs115882574	c.1826 C > T	P609L	Missense	B/LB	< 0.01	9/15	20	0.23	0.06	0.59	3.56	P24	*
NOBOX	rs373109638	c.218 A > G	H73R	Missense	-	< 0.01	3/23	1	0.19	0.36	0	-3.36	P40	*

VEST analysis generates values between 0 and 1, and scores ≥ 0.5 were classified as pathogenic variants and those < 0.5 as benign. CADD analysis generates a PHRED-like scaled value. Scores ≥ 20 were classified as pathogenic variants and those < 20 as benign. PolyPhen analysis generates values between 0 and 1, and scores 0.0 to 0.15 were predicted to be benign, 0.15 to 0.85 as possibly damaging and 0.85 to 1.0 as damaging. The SIFT score ranges from 0 to 1, and scores 0.0 to 0.05 were considered deleterious and 0.05 to 1.0 as tolerated. GERP + + scores range from − 12.3 to 6.17, with higher scores indicating higher evolutionary constraint. A score greater than 2 considered as constrained. Abbreviations: ACMG: American College of Medical Genetics, cDNA: complementary DNA, AA: amino acid change, MAF: minor allele frequency (gnomAD v3.1.2 non-Finnish (controls/biobanks),, P/B: pathogenic/benign prediction.

ISSN: 1755-8794