Table I.
List of variants selected in the Italian POI cohort through targeted-WES.
| Gene | RefSeq | Coding cDNA | Protein | dbSNP | ACMG/AMP guidelines | ID IPOI |
|---|---|---|---|---|---|---|
| ACKR3 d | NM_020311 | c.T1003G | p.S335A | NA | VUS | IPOI28 |
| ADAMTS1 d | NM_006988 | c.C1304A | p.S435Y | rs375553171 | LP | IPOI37 |
| ADAMTS5 d | NM_007038 | c.G2176A | p.G726R | NA | VUS | IPOI03 |
| ADAMTS6 d | NM_197941 | c.G2840A | p.R947Q | rs1272612301 | LP | IPOI36 |
| AFF2 c | NM_001170628 | c.C2126G | p.S709W | rs188208167 | LP | IPOI24 |
| AFP d | NM_001134 | c.G1822A | p.G608R | rs146692547 | LP | IPOI22 |
| ARNTL d | NM_001030272 | c.G18C | p.M6I | NA | VUS | IPOI14 |
| ATG2A d | NM_015104 | c.C1954A | p.L652M | NA | VUS | IPOI40 |
| ATG7 d | NM_001144912 | c.C1144T | p.L382F | NA | VUS | IPOI07 |
| ATG9B d | NM_001317056.1 | c.1480G>T | p.E494X | rs996929151f | LP | IPOI04 |
| BMP6 d | NM_001718 | c.C409Af | p.L137M | rs747427445 | LP | IPOI34 |
| BNC1 a | NM_001301206 | c.C2252T | p.T751I | rs760137127 | LP | IPOI34 |
| BRD3 d | NM_007371 | c.G1149A | p.M383I | NA | VUS | IPOI06 |
| BRDT d | NM_001242807 | c.1400delA | p.D467fs | rs1188709614 | P | IPOI01 |
| BRWD1 d | NM_018963 | c.G656A | p.R219H | rs372595428 | LP | IPOI08 |
| CHEK2 b , e | NM_007194 | c.A1169C | p.Y390S | rs200928781 | P | IPOI20 |
| CYP17A1 c | NM_000102 | c.T644G | p.V215G | rs1428700861 | LP | IPOI37 |
| CYP19A1 c | NM_001347256 | c.A383G | p.H128R | rs375975652 | LP | IPOI22 |
| DMRT3 d | NM_021240 | c.C1327T | p.P443S | rs764103256 | LP | IPOI40 |
| DPPA2 d | NM_138815 | c.T833C | p.L278S | rs1353278679f | LP | IPOI19 |
| FANCA d | NM_000135 | c.C3665T | p.P1222L | rs374537936 | LP | IPOI19 |
| FANCC d | NM_000136 | c.T1027G | p.Y343D | NA | VUS | IPOI10 |
| FYN e | NM_153047 | c.C206G | p.S69C | NA | VUS | IPOI36 |
| GALT d | NM_001258332 | c.C340T | p.R114C | rs111033750 | P | IPOI26 |
| GLI1 d | NM_001160045 | c.T1843C | p.Y615H | NA | VUS | IPOI19 |
| IGF2R d | NM_000876 | c.C451T | p.H151Y | rs756631085 | LP | IPOI36 |
| JAK2 d | NM_004972 | c.G436A | p.D146N | rs1299892808 | P | IPOI45 |
| KDR d | NM_002253 | c.C724T | p.L242F | rs587778428 | LP | IPOI25 |
| KHDRBS1 d | NM_001271878 | c.C1145T | p.P382L | rs750291697 | LP | IPOI02 |
| LARS2 d | NM_015340 | c.A326G | p.D109G | NA | VUS | IPOI36 |
| LEPR d | NM_001198687 | c.C709T | p.P237S | NA | VUS | IPOI28 |
| MECOM d | NM_001163999 | c.G2431A | p.G811S | rs767306816 | LP | IPOI37 |
| MLH3 d | NM_001040108 | c.A1387C | p.S463R | rs138974583 | LP | IPOI33 |
| MOV10 a | NM_001130079 | c.A2831G | p.Y944C | NA | VUS | IPOI09 |
| MYC d | NM_002467 | c.G478A | p.V160I | NA | VUS | IPOI04 |
| NOBOX c | NM_001080413 | c.G1440C | p.K480N | rs1006463439 | LP | IPOI37 |
| NOS3 d | NM_001160109 | c.G505A | p.E169K | rs765854160 | LP | IPOI25 |
| NOS3 d | NM_001160109 | c.C172T | p.P58S | rs752309888 | LP | IPOI26 |
| NOTCH2 d | NM_024408 | c.G5105A | p.R1702Q | rs999822357 | LP | IPOI33 |
| NR5A2 d | NM_001276464 | c.T465G | p.H155Q | rs749896579 | LP | IPOI10 |
| NTRK1 d | NM_001012331 | c.G2101A | p.E701K | rs747855434 | LP | IPOI47 |
| PARD3 a | NM_001184791 | c.C2854G | p.Q952E | NA | VUS | IPOI03 |
| PMM2 c d | NM_000303 | c.C323T | p.A108V | rs200503569 | P | IPOI35 |
| POLG b c | NM_001126131 | c.G1685A | p.R562Q | rs781168350 | LP | IPOI14 |
| POR d | NM_000941 | c.C1588T | p.P530S | rs375387233 | LP | IPOI03 |
| PRIM1 b | NM_000946 | c.G873T | p.W291C | NA | VUS | IPOI40 |
| PRLR d | NM_001204314 | c.T548G | p.L183W | rs748942718 | LP | IPOI21 |
| RAD51C d | NM_058216 | c.A1090G | p.S364G | rs587782565 | LP | IPOI26 |
| RAD54L b | NM_003579 | c.C1138T | p.R380W | rs150138364 | P | IPOI13 |
| RAD54L b | NM_003579 | c.A1883C | p.E628A | NA | LP | IPOI13 |
| RAD54L b | NM_003579 | c.C1900T | p.R634C | rs368491231 | LP | IPOI40 |
| REC8 d | NM_001048205 | c.A1057Cf | p.T353P | NA | VUS | IPOI02 |
| RICTOR d | NM_001285439 | c.A1325G | p.H442R | rs1329438711 | LP | IPOI30 |
| RYR3 a | NM_001036 | c.C2567G | p.T856S | NA | VUS | IPOI02 |
| RYR3 a | NM_001036 | c.A3092T | p.K1031M | rs753104655 | LP | IPOI03 |
| RYR3 a | NM_001036 | c.G6604A | p.A2202T | NA | VUS | IPOI21 |
| SH2B1 d | NM_015503 | c.T1846C | p.S616P | rs142515048 | LP | IPOI12 |
| SIRT6 a | NM_001321058 | c.G146A | p.R49H | rs771714154 | LP | IPOI44 |
| STAG3 c | NM_001282718 | c.C895T | p.R299X | rs774733445 | P | IPOI36 |
| THBS1 d | NM_003246 | c.C1060T | p.P354S | rs142519614 | LP | IPOI01 |
| WHAMM a | NM_001080435 | c.C734T | p.P245L | NA | VUS | IPOI01 |
| WT1 d | NM_000378 | c.A970G | p.S324G | rs121907908g | LP | IPOI36 |
| XPNPEP2 d | NM_003399 | c.G1081A | p.E361K | NA | VUS | IPOI03 |
| ZNF462 d | NM_021224 | c.C3515G | p.P1172R | rs1469441260 | LP | IPOI21 |
All variants reported had frequencies significant for Fisher Exact Test or were never reported in the population databases investigated (1000G, ExAC and gnomAD).
Genes identified through array-CGH analysis of primary amenorrhoea patients (Bestetti et al., 2019).
Menopausal genes (Colonna et al., 2013).
OMIM POI genes or genes previously associated to POI.
Other ovary-related genes(Colonna et al., 2013; Patiño et al., 2017).
Interactor of the most promising candidates from previous array-CGH analysis (Bestetti et al., 2019).
BMP6: homozygous variant; REC8: compound heterozygous variant.
Frequency reported in dbSNP with <0.00001 MAF.
dbSNP, single-nucleotide polymorphism database; LP, likley pathogenic; MAF, minor allele frequency; NA, not available; P, pathogenic; POI, primary ovarian insufficiency; VUS, variant of uncertain significance.