Table 3.
Correlation among severity, phenotype and pathogenicity predictions in patients with 4 variants in potentially POI genes.
| Patients ID | Origin | Karyotype | Phenotype | Menarche(yrs) | POI onset(yrs) | Familiarity | Variation(HGVS) | Zigosity | OVO-Array patients’ frequency (n = 64) | gnomAD ver. 2.1.1 female population frequency | VarSome predictionv.2.1.1 | VarSome Criteria |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 6 | Caucasian | not available | OD | No | – | Yes | FIGLA(NM_001004311.3):c.364del:(p.Glu122LysfsTer45) | Het | 0.015625 | Novel | P | PVS1,PM2,PP5,PP3 |
| NOBOX(NM_001080413.3):c.1626del:(p.Phe543SerfsTer7) | Het | 0.015625 | Novel | P | PVS1,PM2,PP5 | |||||||
| NR5A1(NM_004959.5):c.1063G>A:(p.Val355Met) | Het | 0.03125 | 0.000122 | LP | PM1,PM2,PP5,PP2,PP3 | |||||||
| NCOR2(NM_006312.6):c.3755C>A:(p.Pro1252Gln) | Het | 0.015625 | Novel | VUS | PM2,PP3 | |||||||
| 7 | Caucasian | not available | PA | No | – | No | VWF(NM_000552.5):c.4517C>T:(p.Ser1506Leu) | Het | 0.046875 | – | P | PP5,PM1,PM2,PP2,PP3 |
| VWF(NM_000552.5):c.4508T>C:(p.Leu1503Pro) | Het | 0.03125 | Novel | LP | PM1,PM2,PM5,PP2,PP3 | |||||||
| NOTCH3(NM_000435.3):c.2791A>G:(p.Ser931Gly) | Het | 0.015625 | Novel | LP | PM1,PM2,PP2,PP3 | |||||||
| TRRAP(NM_001244580.1):c.10171A>G:(p.Met3391Val) | Het | 0.015625 | Novel | VUS | PM2,PP2 | |||||||
| 8 | Caucasian | not available | eSA | 16 | 18 | No | SAMD11(NM_152486.4):c.682_683insT: (p.Pro228LeufsTer227) |
Het | 0.09375 | 0.000183 | LB | BS1 |
| ATG4C(NM_032852.4):c.607dup: (p.Trp203LeufsTer4) | Het | 0.015625 | 0.000659 | VUS | PP3,BS1 | |||||||
| NOTCH4(NM_004557.4):c.2945C>T:(p.Thr982Ile) | Het | 0.015625 | Novel | VUS | PM2,PP3,BP1 | |||||||
| RMI1(NM_024945.3):c.746C>T:(p.Ala249Val) | Het | 0.015625 | Novel | VUS | PM2,PP3 | |||||||
| 9 | Caucasian | not available | eSA | 14 | 14 | No | NR5A1(NM_004959.5):c.502G>C:(p.Ala168Pro) | Het | 0.015625 | Novel | VUS | PM2,PP2,BP4 |
| SYNE1(NM_182961.4):c.16709A>G:(p.Gln5570Arg) | Het | 0.015625 | Novel | LP | PP3,PM2 | |||||||
| RAD50(NM_005732.4):c.2165dup:(p.Glu723GlyfsTer5) | Het | 0.015625 | 0.000301 | P | PVS1,PP5,PM2,PP3 | |||||||
| ADAMTS5(NM_007038.5):c.1729G>A:(p.Gly577Ser) | Het | 0.03125 | 0.0151 | VUS | PP3,BS1 | |||||||
| 10 | Caucasian | 46,XX | SA | 13 | 25 | – | ADAMTS4(NM_005099.6):c.803G>A:(p.Arg268Gln) | Het | 0.015625 | – | VUS | PM2,BP4 |
| DHCR24(NM_014762.4):c.1046C>G:(p.Pro349Arg) | Het | 0.015625 | 0.0000087 | VUS | PM2,PP2,PP3 | |||||||
| FSHR(NM_000145.4):c.491C>T:(p.Ser164Phe) | Het | 0.015625 | Novel | VUS | PM2,PP2,PP3 | |||||||
| RAD52(NM_134424.4):c.175G>A:(p.Gly59Arg) | Het | 0.015625 | 0.000699 | VUS | PP3 | |||||||
| 11 | Caucasian | 46,XX | SA | 11 | 14 | No | APC2(NM_005883.3):c.2887C>T:(p.Arg963Trp) | Het | 0.015625 | 0.0000135 | VUS | PM2,PP3,BP1 |
| ATG2A(NM_015104.3):c.4414G>C:(p.Gly1472Arg) | Het | 0.015625 | 0.0000174 | VUS | PM2,PP3,BP1 | |||||||
| COL6A1(NM_001848.3):c.350T>C:(p.Val117Ala) | Het | 0.015625 | 0.000982 | VUS | PM2,PP2,PP3 | |||||||
| KPNA2(NM_002266.4):c.445T>C:(p.Ser149Pro) | Het | 0.015625 | Novel | VUS | PM2.PP3 | |||||||
| 12 | Caucasian | not available | SA | 11 | 25 | No | LARS2(NM_015340.4):c.2192A>T:(p.Tyr731Phe) | Het | 0.015625 | Novel | VUS | PM2,PP2,BP4 |
| RBBP8(NM_002894.3):c.2516G>A(p.Arg839Gln) | Het | 0.03125 | 0.000415 | VUS | PM2,PP3,BP1 | |||||||
| THBS2(NM_003247.5):c.1183G>A:(p.Val395Met) | Het | 0.015625 | 0.0000528 | VUS | PP3,BS1,BP1 | |||||||
| RIPK1(NM_003804.6):c.700G>A:(p.Glu234Lys) | Het | 0.015625 | 0.000684 | VUS | PM2,PP2,BP4,BP6 | |||||||
| 13 | Caucasian | not available | SA | 12 | 21 | No | ATM(NM_000051.4):c.7375C>T:(p.Arg2459Cys) | Het | 0.015625 | 0.0000433 | VUS | PM1,PM2,PP3 |
| NCOR2(NM_006312.6):c.3709G>A:(p.Val1237Ile) | Het | 0.015625 | 0.00000886 | VUS | PP3 | |||||||
| POLG(NM_001126131.2):c.752C>T:(p.Thr251Ile) | Het | 0.03125 | 0.00147 | LP | PS3,PM2,PP2,PP5 | |||||||
| POLG(NM_001126131.2):c.1760C>T:(p.Pro587Leu) | Het | 0.03125 | 0.0015 | P | PP5,PS3,PM2,PP2,PP3 | |||||||
| 14 | Caucasian | 46,XX | SA | 12 | 16 | Yes | VWF(NM_000552.5):c.4517C>T:(p.Ser1506Leu) | Het | 0.046875 | Novel | P | PP5,PM1,PM2,PP2,PP3 |
| VWF(NM_000552.5):c.5641G>A:(p.Asp1881Asn) | Het | 0.015625 | Novel | VUS | PM2,PP2,PP3 | |||||||
| LGR4(NM_018490.5):c.2531A>G:(p.Asp844Gly) | Het | 0.015625 | 0.0124 | VUS | PP3,BS1,BP1,BP6 | |||||||
| HK3(NM_002115.3):c.2389G>A:(p.Glu797Lys) | Het | 0.015625 | 0.000113 | VUS | PP3,BS1,BP1 |
OD, ovarian dysgenesis; PA, primary amenorrhea; eSA, early secondary amenorrhea; SA, secondary amenorrhea; Het, heterozygosity; P, pathogenic; VUS, variant of unknown significance; LP, likely pathogenic; LB, likely benign.