Table 5.
Correlation among severity, phenotype and pathogenicity predictions in patients with 2 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 24 | African | 46,XX | OD | No | – | Yes | NOBOX(NM_001080413.3):c.1112A>C:(p.Lys371Thr) | Het | 0.015625 | – | B | BS1,BS2,BP1,BP4 |
| STAG3(NM_012447.4):c.1079G>A:(p.Arg360His) | Het | 0.015625 | – | LP | PM1,PM2,PP2,PP3 | |||||||
| 25 | African | not available | PA | No | – | No | REC8(NM_005132):c.899G>T:(p.Arg300Leu) | Het | 0.015625 | 0.00234 | VUS | PPP3,BS1 |
| LHCGR(NM_000233):c.C568A:(p.Gln190Lys) | Het | 0.015625 | 0.000563 | VUS | PM2,PP2,BP6 | |||||||
| 26 | Caucasian | 46,XX | PA | No | – | Yes | AGRN(NM_198576.4):c.2860G>A:(p.Ala954Thr) | Het | 0.015625 | 0.000026 | VUS | PM2,PP3,BP1 |
| VLDLR(NM_003383.5):c.902G>A:(p.Arg301Gln) | Het | 0.015625 | 0.00192 | VUS | PM2,BP1 | |||||||
| 27 | Caucasian | 46,XX | PA | No | – | Yes | TP63(NM_003722.5):c.1927C>T:(p.Arg643Ter) | Het | 0.015625 | Novel | P | PVS1,PM2,PP3,PP5 |
| FANCA(NM_000135.4):c.1340C>T:(p.Ser447Leu) | Het | 0.015625 | 0.000486 | VUS | PM2,PP2,PP3 | |||||||
| 28 | Caucasian | 46,XX | eSA | 12 | 13 | No | DMRT3(NM_021240.4):c.897dup:(p.Ala300ArgfsTer4) | Het | 0.015625 | – | P | PVS1,PM2,PP3 |
| RELN(NM_005045.4):c.2015C>T:(p.Pro672Leu) | Het | 0.015625 | 0.000139 | LP | PM1,PM2,PP3,PP5,BP1 | |||||||
| 29 | Caucasian | 46,XX | eSA | 13 | 13 | No | HDAC5(NM_001015053.2):c.446A>G:(p.Glu149Gly) | Het | 0.015625 | – | VUS | PM2,PP3,BP1 |
| AKAP9(NM_005751.5):c.4351A>G:(p.Met1451Val) | Het | 0.015625 | – | VUS | PM2,PP3,BP1 | |||||||
| 30 | Caucasian | 46,XX | SA | 9 | 22 | Yes | SAMD11(NM_152486.4):c.682_683insT: (p.Pro228LeufsTer227) |
Het | 0.09375 | 0.000183 | LB | BS1 |
| HK3(NM_002115.3):c.2077A>C:(p.Met693Leu) | Het | 0.015625 | 0.000165 | LB | PP3,BS1,BP1 | |||||||
| 31 | Caucasian | 46,XX | SA | 12 | 22 | not available | CCNB1IP1(NM_182852.3):c.454G>A:(p.Glu152Lys) | Het | 0.015625 | Novel | VUS | PM2,BP4 |
| MLH3(NM_001040108.2):c.3943G>A:(p.Glu1315Lys) | Het | 0.015625 | – | VUS | PM2,PP3,BP1 | |||||||
| 32 | Caucasian | 46,XX | SA | 13 | 15 | No | MSH4(NM_002440.4):c.1286A>T:(p.Glu429Val) | Het | 0.015625 | Novel | VUS | PM2,PP3 |
| CYP21A2(NM_000500.9):c.844G>T:(p.Val282Leu) | Het | 0.03125 | Novel | VUS | PP2,PP3 | |||||||
| 33 | Caucasian | 46,XX | SA | 10 | 17 | No | SAMD11(NM_152486.4):c.628C>T:(p.Arg210Cys) | Het | 0.015625 | 0.000536 | LB | PP3,BS1,BP1,BP6 |
| COL6A2(NM_001849.4):c.2575G>A:(p.Val859Met) | Het | 0.015625 | 0.000241 | VUS | PM2,PP2 | |||||||
| 34 | Caucasian | 46,XX | SA | 10 | 25 | No | GPR137C(NM_001099652.2):c.1211A>G:(p.Asp404Gly) | Het | 0.015625 | Novel | VUS | PM2,BP4 |
| RELN(NM_005045.4):c.3651C>G:(p.Ile1217Met) | Het | 0.015625 | 0.00255 | VUS | PM2,PP3,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; B, benign.