Table 2.
Genetic causes of DSD in patients from the Ukraine DSD Register.
| Gene | Patient | Variant | Zygosity | MAF (population) | ClinVar (Variation ID) | Pathogenicity (ACMG) |
|---|---|---|---|---|---|---|
| AR | 1 | p.I836S | Hemi | Novel | NA | Pathogenic |
| AR | 2 | p.N706S | Hemi | Novel | NA | Pathogenic |
| AR | 3 | p.N706S | Hemi | Novel | NA | Pathogenic |
| AR | 4 | p.H886L | Hemi | Novel | NA | Pathogenic |
| AR | 5 | p.Q799E | Hemi | 0.002741 (European) | Likely pathogenic (9846) | Likely Pathogenic |
| AR | 6 | c.2607+2T>G | Hemi | Novel | NA | Pathogenic |
| AR | 7, 8 (siblings) | p.I843T | Hemi | Novel | NA | Pathogenic |
| AR | 9 | p.Leu839Ile | Hemi | Novel | NA | Likely Pathogenic |
| AR | 10 | p.Arg841Cys | Hemi | Novel | NA | Pathogenic |
| AR | 11 | p.Arg775His | Hemi | Novel | NA | Pathogenic |
| NR5A1 | 12, 13 (siblings) | c.244+1G>T | Het | Novel | NA | Pathogenic |
| NR5A1 | 14 | p.C73Y | Het | Novel | NA | Pathogenic |
| NR5A1 | 15 | G35D | Het | Novel | NA | Pathogenic |
| NR5A1 | 16 | p.C73W | Het | Novel | NA | Pathogenic |
| AMHR2 | 17,18 (siblings) | p.R463H/p.R471H | Compound Het | Novel/Novel | NA/NA | Pathogenic |
| HSD17B3 | 19 | p.E215D/c.277+4A>T | Compound Het | 0.00009289 (European)/0.0006822 (European) | NA/Pathogenic (208587) | Pathogenic |
| HSD17B3 | 20 | p.M47V/p.V243fs | Compound Het | 0.00008516 (European)/Novel | Pathogenic | |
| MYRF | 21 | p.N105D | Het | Novel | NA | Likely Pathogenic |
| MYRF | 22 | c.2572+1G>A | Het | Novel | NA | Likely Pathogenic |
| ANOS1 | 23 | p.Gln586 | Hemi | Novel | NA | Pathogenic |
| ANOS1 | 24, 25 (cousins) | p.Gln57fs* | Hemi | Novel | NA | Pathogenic |
| FGFR1 | 26 | c.179_208del; p.Asp60_Asp69del | Het | Novel | NA | Likely Pathogenic |
| WT1 | 27 | p.S255L | Het | Novel | NA | Likely Pathogenic |
| DHX37 | 28 | p.R674Q | Het | Novel | NA | Pathogenic |
| SRD5A2 | 29 | p.Y91H/p.G13R | Compound Het | 0.0001913 (other)/Novel | Pathogenic (492899)/NA | Pathogenic |
| GATA4 | 30 | p.G12R | Het | 0.00003898 (European) | Uncertain significance (644697) | Likely pathogenic |
| TBCE | 31 | c.100+1G>A | Homozygous | Novel | NA | Likely pathogenic |
| CYP19A1 | 32 | p.R457X/p.Leu353fs | Compound Het | 0.00009800 (South Asian)/0.000008829 (European) | NA/Pathogenic (653853) | Pathogenic |
| CACNA1A | 33 | p.I219V | Het | Novel | NA | Pathogenic |
| GLI2 | 34 | p.E1577K | Het | 0.0009526 (East Asian) | Likely benign; Uncertain significance (798233) | Likely pathogenic |
| VUS, Pathogenicity by ACMG | ||||||
| Gene | Patient | Variant | Zygosity | MAF (population) | ClinVar (Variation ID) | Preliminary clinical diagnosis |
| ABCD1 | 15 | p.M539V | Het | Novel | NA | 46XY, U |
| ESR2 | 33 | p.Y49C | Het | Novel | NA | 46XY, ovotesticular DSD |
| WT1 | 35 | p.T474T | Het | Novel | NA | 46XX, testicular DSD |
| CBX2 | 36 | p.R135Q | Het | Novel | NA | 46XY, GD |
| POMC | 37 | p.A100delinsSSGSSGA | Het | 0.0003894 (African) | NA | 46XY, TRS |
| HSD17B13 | p.S165X/p.S201X | Compound het | Novel/Novel | NA/NA | ||
| SPRY4 | 38 | p.L283M | Het | Novel | NA | 46XY, GD |
| FLRT3 | p.T61R | Het | Novel | NA | ||
| FANCL | p.Thr372fs | Het | 0.006795 (Ashkenazi/Jewish) | Benign; Pathogenic; Uncertain significance (210988) | ||
| DHX37 | 39 | p.G1030E | Het | Novel | NA | 46XY, TRS |
| SRCAP | 40 | p.S1747delinsSLAPAPP | Het | Novel | NA | 46XY, U, AG |
| WDR34 | 41 | p.Q158X | Het | 0.00004054 (European) | Pathogenic (97044) | 46XY, U, AG |
| WDR35 | p.T1020R | Het | 0.001015 (European) | Uncertain significance (333372) | ||
| DYNC2H1 | p.S2281C | Het | 0.00009968 (Ashkenazi/Jewish) | NA | ||
| CDT1 | p.R138W | Het | 0.0003477 (European) | Uncertain significance (1044530) | ||
| TRAF3IP1 | p.I386V | Het | Novel | NA | ||
| SOX4 | p.A275V | Het | Novel | NA | ||
| CCDC141 | 42 | p.Y1081_G1082delinsX | Homozygous | Novel | NA | 46XY, U, AG |
| WDR11 | 43 | p.F1150L/p.V356I | Compound het | 0.008582 (Ashkenazi/Jewish) 0.002965 (European) | Likely benign; Uncertain significance (68842) Likely benign (695236) | 46XY, U, AG |
| MYRF | p.A315V | Het | 0.0001634 (South Asian) | NA | ||
| ANOS1 | c.856+3C>T | Hemi | Novel | NA | ||
| CCDC141 | p.D767N | Het | 0.006612 (European Finnish) | Likely benign (638188) | ||
| FSHR | 44 | p.S498R/p.S524R | Compound het | Novel/Novel | NA | 46XY, TRS |
| AMH | 45 | p.D288E | Het | 0.002311 (European) | NA | 46XY, PAIS |
| HESX1 | 46 | p.V129I | Het | 0.001744 (Ashkenazi/Jewish) | Likely benign; Uncertain significance (26773) | 46XY, U |
| POU1F1 | p.D10G | Het | Novel | NA | ||
| LHCGR | 47 | p.540_540delF | Het | 0.00002892 (Latino) | NA | 46XY, U, AG |
| CYP19A1 | 48 | c.451+2T>A | Het | Novel | NA | 46XY, U, AG |
| POU1F1 | 49 | p.D10G | Het | Novel | NA | 46XY, U, AG |
| GNRHR | p.P146S | Het | 0.004587 (other) | Likely benign; Uncertain significance (449413) | ||
| GATA4 | 50 | p.P163S | Het | 0.0006612 (East Asian) | Pathogenic; Uncertain significance (30099) | 46XX, U, AG |
| GALT | 51 | p.P66L | Het | 0.00006972 (European) | Uncertain significance (25136) | 46XX, PH |
| TACR3 | p.A449S | Het | 0.0003724 (European) | Uncertain significance (436936) | ||
| LETM1 | c.1200+4C>T | Het | 0.0002957 (European) | NA | ||
| NIN | p.K2057Q | Het | Novel | NA | ||
| STAR | 52 | p.D163N | Het | 0.00008689 (Latino) | NA | 46XY, GD (seminoma) |
| SAMD9 | 53 | p.R1040C | Het | 0.00009308 (European) | NA | 46XY, TRS, Severe immunodeficiency |
| STAT1 | c.1632+6G>A | Het | 0.0003951 (European) | Benign; Uncertain significance (333271) | ||
| IKBKB | p.A755S | Het | 0.001372 (South Asian) | Likely benign (746609) | ||
| TAP2 | p.L59delinsLKLRGLL | Het | Novel | NA | ||
| HSD3B2 | 54 | p.A167V | Het | 0.003724 (South Asian) | Benign; Uncertain significance (724290) | 46XY, GD (gonadoblastoma) |
| FANCM | p.Ser497fs | Het | 0.000008804 (European) | NA | ||
| PTCH1 | 55 | p.T627M | Het | Novel | NA | 46XY, U, AG |
| LZTR1 | p.M695I | Het | Novel | NA | ||
| HSD17B3 | 56 | p.G97A | Het | 0.00001758 (European) | NA | 46XY, U, AG |
| LHCGR | 57 | p.Y113N | Het | 0.006076 (Ashkenazi/Jewish) | Benign; Likely benign; Uncertain significance (336469) | 46XY, CAIS |
| LHX3 | p.A3V | Het | 0.001396 (European) | Likely benign; Uncertain significance (279836) | ||
| GNAS | p.A426P | Het | 0.00008206 (European) | Likely benign (931358) | ||
| PAX4 | p.C282R | Het | 0.002110 (European) | Likely benign (436159) | ||
| HHAT | 58 | p.V399fs | Het | Novel | NA | 46XY, GD (dysgerminoma) |
| AMH | 59 | p.T22A | Het | 0.00006401 (Latino/Admixed American) | NA | 46XY, TRS |
| CHD7 | 60 | p.M2527L | Het | 0.003603 (European) | Likely Benign (158317) | 46XY, TRS |
| ANOS1 | c.256-2A>T | Hemi | Novel | NA | ||
| WDR11 | 61 | p.A435T | Het | 0.0004573 (South Asian) | Pathogenic (37309) | 46XY, GD (gonadoblastoma) |
| WDR11 | 62 | p.A435T | Het | 0.0004573 (South Asian) | Pathogenic (37309) | 46XY, TRS |
| CHD7 | p.M340V | Het | 0.009463 (Ashkenazi/Jewish) | Likely Benign (95773) | ||
| POR | p.V348I | Het | 0.00004061 (European) | Uncertain significance (910412) | ||
NA, Not Applicable.