Table 4.
Correlation among severity, phenotype and pathogenicity predictions in patients with 3 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 15 | Caucasian | not available | PA | 9 | 9 | Yes | TEX15(NM_001350162.2):c.6511C>T:(p.Arg2171Ter) | Het | 0.015625 | 0.0000175 | p | PVS1,PM2,PP3 |
| TUBA8(NM_018943.3):c.967G>A:(p.Val323Met) | Het | 0.015625 | 0.000243 | VUS | PM2,PP3,BP1 | |||||||
| ID1(NM_002165.4):c.458_460del:(p.Leu153del) | Het | 0.015625 | 0.00000886 | VUS | PM2,PM4,BP4 | |||||||
| 16 | Caucasian | not available | PA | – | – | No | ATR(NM_001184.4):c.4610T>A:(p.Leu1537Ter) | Het | 0.015625 | Novel | P | PVS1,PM2,PP3 |
| POLG(NM_001126131.2):c.1760C>T:(p.Pro587Leu) | Het | 0.03125 | 0.0015 | P | PP5,PS3,PM2,PP2,PP3 | |||||||
| POLG(NM_001126131.2):c.752C>T:(p.Thr251Ile) | Het | 0.03125 | 0.00147 | LP | PS3,PM2,PP2,PP5 | |||||||
| 17 | Caucasian | 46,XX | eSA | 12 | 12 | No | NOTCH2(NM_024408.4):c.2084C>A:(p.Ala695Glu) | Het | 0.015625 | Novel | VUS | PM2,PP3 |
| TP53(NM_001126114.2):c.475G>A:(p.Ala159Thr) | Het | 0.015625 | – | P | PM1,PM2,PM5,PP2,PP3 | |||||||
| SAMD11(NM_152486.4):c.682_683insT: (p.Pro228LeufsTer227) |
Het | 0.09375 | 0.000183 | LB | BS1 | |||||||
| 18 | Caucasian | 46,XX | SA | 13 | 19 | No | ERBB3(NM_001982.4):c.2269dup:(p.Thr757AsnfsTer70) | Het | 0.015625 | Novel | P | PVS1,PM2,PP3 |
| POLG(NM_001126131.2):c.803G>C:(p.Gly268Ala) | Het | 0.015625 | 0.00339 | VUS | PP2,PP3,PP5,BS2 | |||||||
| LARS2(NM_015340.4):c.457A>C:(p.Asn153His) | Het | 0.015625 | – | LP | PP3,PM2,PP2,PP5 | |||||||
| 19 | Caucasian | 46,XX | SA | 14 | 23 | No | RAD52(NM_134424.4):c.388G>A:(p.Glu130Lys) | Het | 0.015625 | 0.000138 | VUS | PP3 |
| RBBP8(NM_002894.3):c.2516G>A:(p.Arg839Gln) | Het | 0.03125 | 0.000415 | VUS | PM2,PP3,BP1 | |||||||
| PLEC(NM_201380.4):c.5801G>A:(p.Arg1934His) | Het | 0.015625 | 0.000128 | VUS | PM2,PP3,BP1 | |||||||
| 20 | Caucasian | 46,XX | SA | 13 | 22 | No | ATG4C(NM_032852.4):c.774_777del:(p.Ile258MetfsTer13) | Het | 0.015625 | 0.0000546 | VUS | PP3,BS1 |
| ATM(NM_000051.4):c.4829G>C:(p.Arg1610Thr) | Het | 0.015625 | Novel | VUS | PM2,PP3 | |||||||
| PRIM1(NM_000946.3):c.911G>T:(p.Arg304Leu) | Het | 0.015625 | Novel | VUS | PM2,PP3 | |||||||
| 21 | Caucasian | 46,XX | SA | not available | 19 | No | SAMD11(NM_152486.4):c.682_683insT: (p.Pro228LeufsTer227) |
Het | 0.09375 | 0.000183 | LB | BS1 |
| KMT2D(NM_003482.4):c.10876C>T:(p.Arg3626Trp) | Het | 0.015625 | – | VUS | PM2,PP3 | |||||||
| NBN(NM_002485.5):c.596C>G:(p.Pro199Arg) | Het | 0.015625 | – | VUS | PM2,PP3 | |||||||
| 22 | Caucasian | 46,XX | SA | not available | 20 | No | COL6A2(NM_001849.4):c.343C>T:(p.Arg115Trp) | Het | 0.015625 | 0.00000873 | VUS | PM2,PP2,PP3 |
| LRP5(NM_002335.4):c.4511C>T:(p.Pro1504Leu) | Het | 0.015625 | 0.000389 | VUS | PM2,PP2,PP3,BP6 | |||||||
| APC2(NM_005883.3):c.932C>T:(p.Ser311Leu) | Het | 0.015625 | – | VUS | PM2,PP3,BP1 | |||||||
| 23 | Caucasian | 46,XX | SA | 14 | 16 | not available | BMP15(NM_005448.2):c.202C>T:(p.Arg68Trp) | Het | 0.015625 | 0.000708 | B | PM1,PP3,PP5,BS1,BS2,BP1 |
| GDF9(NM_005260.5):c.1121C>T:(p.Pro374Leu) | Het | 0.015625 | 0.0000346 | VUS | PM2,PP3,BP6 | |||||||
| GDF9(NM_005260.5):c.278A>G:(p.Tyr93Cys) | Het | 0.015625 | Novel | VUS | PM1,PM2,PP3 |
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.