Table 2.

Candidate variants identified in POI families (POI 1–7) and oocyte donors (D1 and D2)

Family/Donor ID	Gene	Transcript	dsSNP	Nucleotide variation	Amino acid change	Effect	GnomAD	S/P/M	ACMG score	ACMG classification
POI 1	CSMD1	NM_033225.5	rs1435513451	c.5844 + 3A > G	-	Splice region	0.000072	-	PM2/PP3	VUS
	CASP2	NM_032982.3	rs1026228070	c.1144C > T	p.Arg382Ter	Stop gain	0.000029	D/-/D	PM2/PVS1	Likely pathogenic
POI 2	XPC	NM_004628.4	rs1346001152	c.2306 T > C	p.Ile769Thr	Missense	0	D/B/D	PM2	VUS
	RXFP2	NM_130806.3	rs150652160	c.1826A > G	p.Tyr609Cys	Missense	0.001	D/D/D	PM2/BS2	VUS
POI 3	ROBO1	NM_002941.3	rs375897144	c.703G > A	p.Ala235Thr	Missense	0.0001	T/D/D	PM2	VUS
	HOXA1	NM_005522.4	-	c.62G > A	p.Gly21Glu	Missense	0	D/D/D	PM2	VUS
	VWF	NM_000552.4	rs376285757	c.8324C > T	p.Ser2775Phe	Missense	0.00002	D/B/D	PM2/PP2	VUS
	TPM1	NM_001018005.1	rs397516376	c.548C > T	p.Ala183Val	Missense	0.00004	D/D/D	PM2/PM1/PP2/PP3/PP5	Likely pathogenic
	PIWIL3	NM_001008496.3	rs142590557	c.727C > T	p.Arg243Cys	Missense	0.00072	D/D/-	PM2	VUS
POI 4	TTI2	NM_025115.3	rs140977711	c.1135C > T	p.Arg379Trp	Missense	0.0001	D/D/D	PM2	VUS
	NFKB2	NM_001077494.3	rs200139098	c.1993A > T	p.Thr665Ser	Missense	0.00023	D/D/D	PM2/PP2	VUS
	VDR	NM_001017536.1	rs756858031	c.479G > A	p.Arg160Gln	Missense	0.00011	T/D/D	PM2	VUS
	MTNR1A	NM_005958.4	rs138837121	c.1002A > T	p.Lys334Asn	Missense	0.0022	D/D/D	PM2/BS2	VUS
	EFNA5	NM_001962.2	-	c.168C > A	p.Asp56Glu	Missense	0	D/D/D	PM2/PP3	VUS
	DLL1	NM_005618.3	rs776343632	c.2167-3del	-	Splice region	0.0018	-	BS1	VUS
	JAG1	NM_000214.2	rs375017114	c.1627C > T	p.Arg543Cys	Missense	0.00007	D/D/D	PM2/PP2	VUS
	VWF	NM_000552.4	rs368366214	c.3101_3103del	p.Thr1034del	Inframe deletion	0.0002	-	PM4/BS1	VUS
POI 5	PTH1R	NM_000316.2	-	c.822_831del	p.Ala275ThrfsTer8	Frameshift	0	-	PVS1/PM2	Likely pathogenic
	HSD3B1	NM_000862.2	rs775120619	c.258 T > G	p.Ile86Met	Missense	0.00008	D/D/D	PM2	VUS
	SLC6A9	NM_201649.3	rs757420753	c.577G > A	p.(Gly193Ser)	Missense	0.00002	T/D/D	PM2	VUS
	GLO1	NM_006708.2	rs141465532	c.383 T > C	p.(Ile128Thr)	Missense	0.0003	D/D/D	PM2	VUS
POI 6	PCM1	NM_006197.3	rs148806955	c.4057G > T	p.Glu1353Ter	Stop gain	0.003	-	PM2	VUS
POI 7	DDX11	NM_152438.1	rs2111769	c.1242 + 4 T > C	-	Splice region	0.000008	-	BP4	VUS
D1	PIWIL3	NM_001008496.3	rs747731185	c.106del	p.Gln36ArgfsTer41	Frameshift	0.0016	-	PM2	VUS
D2	VWF	NM_000552.4	rs1800386	c.4751A > G	p.Tyr1584Cys	Missense	0.004	D/D/D	PM2/PP2/PP5	Likely pathogenic
	CSMD1	NM_033225.5	rs763163101	c.8926G > A	p.Val2976Met	Missense	0.00002	D/D/D	PM2	VUS

GnomAD, the variant frequency in the genomAD database for non-Finish European population; S/P/M, The prediction of SIFT/Poyphen2/MutationTaster bioinformatics tools (SIFT D, deleterious; T, tolerated/Polyphen2; D, probably damaging; B, benign/MutationTaster; D, disease causing). ACMG, American College of Medical Genetics