Table 3 Oligogenic variants in our cohort
Patient’s ID | Phenotype | Number of genes | Number of variants | Gene | Gene category | Transcript | Nucleotide change | Amino acid change | Variant type | Heterozygosity | Pathogenicity | Inheritance | Reference(PMID) | ORVAL prediction | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Combination | VarCoPP score | Predicted pathogenicity | ||||||||||||||
DSD-0009 | Micropenis, Cryptorchidism(bilateral) | 3 | 3 | PROKR2 | synthesis or action of androgen | NM_144773 | c.G491A | p.R164Q | Missense | Het | P | De novo | 18,826,963 | FGFR1/ PROKR2 | 0.98 | Disease-causing with 99.9% confidence |
DSD-0009 |  |  |  | FGFR1 | synthesis or action of androgen | NM_023110 | c.1664-1G > T |  | Splicing | Het | LP | De novo | novel | FGFR1/CYP11B1 | 0.835 | Disease-causing with 99% confidence |
DSD-0009 | Â | Â | Â | CYP11B1 | synthesis and activation of Steroid hormone | NM_000497 | c.G779A | p.W260X | Nonsense | Het | P | De novo | 28,962,970 | CYP11B1/PROKR2 | 0.7975 | Disease-causing with 99% confidence |
DSD-0115 | Micropenis, Cryptorchidism(right), inguinal hernia | 2 | 2 | PROKR2 | synthesis or action of androgen | NM_144773 | c.G533C | p.W178S | Missense | Het | P | De novo | 36,317,218 | Â | 0.7425 | Candidate disease-causing |
DSD-0115 | Â | Â | Â | ATRX | Syndromic disorders | NM_138270 | c.C4643T | p.P1548L | Missense | Hemi | VUS | unknown | novel | Â | Â | Â |
DSD-0260 | Micropenis | 2 | 2 | PROKR2 | synthesis or action of androgen | NM_144773 | c.G533C | p.W178S | Missense | Het | P | De novo | 36,317,218 | PROKR2/AR | 0.92 | Disease-causing with 99% confidence |
DSD-0260 | Â | Â | Â | AR | synthesis and activation of Steroid hormone | NM_000044 | c.A179T | p.Q60L | Missense | Hemi | VUS | Mother | 26,804,919 | Â | Â | Â |
DSD-0260 | Â | Â | Â | ATRX | synthesis and activation of Steroid hormone | NM_138270 | c.A2352C | p.E784D | Missense | Hemi | VUS | Mother | VCV002191696.1 | Â | Â | |
DSD-0122 | Micropenis | 3 | 3 | FGFR1 | synthesis or action of androgen | NM_001174063 | c.246_247del | p.E84Gfs*26 | frameshift deletion | Het | P | De novo | novel | FGFR1/LHCGR | NA | No combination |
DSD-0122 | Â | Â | Â | LHCGR | synthesis and activation of Steroid hormone | NM_000233 | c.135delC | p.G46Afs*18 | frameshift deletion | Het | VUS | De novo | novel | LHCGR/POR | NA | No combination |
DSD-0122 | Â | Â | Â | POR | synthesis and activation of Steroid hormone | NM_000941 | c.G1370A | p.R457H | Missense | Het | VUS | unknown | 36,518,257 | FGFR1/POR | 0.9225 | Disease-causing with 99.9% confidence |
DSD-0088 | hypospadias | 2 | 2 | FGFR1 | synthesis or action of androgen | NM_001174063 | c.T20G | p.L7R | Missense | Het | VUS | unknown | 37,805,574 | Â | 0.98 | Disease-causing with 99.9% confidence |
DSD-0088 | Â | Â | Â | NR5A1 | development and differentiation of gonadal | NM_004959 | c.C1019T | p.A340V | Missense | Het | VUS | unknown | 30,668,521 | Â | Â | Â |
DSD-0352 | Micropenis, Cryptorchidism(bilateral) | 2 | 2 | GATA4 | development and differentiation of gonadal | NM_001308093 | c.35_36insGCC | p.P15_G16insP | frameshift insertion | Het | LP | unknown | novel | Â | 0.9775 | Disease-causing with 99.9% confidence |
DSD-0352 | Â | Â | Â | NR5A1 | development and differentiation of gonadal | NM_004959 | c.G1333A | p.E445K | Missense | Het | VUS | unknown | novel | Â | Â | Â |
DSD-0323 | Micropenis | 2 | 2 | AR | synthesis and activation of Steroid hormone | NM_000044 | c.C1219G | p.R407G | Missense | Hemi | LP | Mother | novel | Â | 0.9925 | Disease-causing with 99.9% confidence |
DSD-0323 | Â | Â | Â | WNT4 | development and differentiation of gonadal | NM_030761 | c.G847A | p.D283N | Missense | Het | VUS | unknown | novel | Â | Â | Â |
DSD-0328 | hypospadias | 2 | 2 | SOS1 | Syndromic disorders | NM_005633 | c.C1410A | p.C470X | Nonsense | Het | LP | unknown | novel | Â | 0.9125 | Disease-causing with 99.9% confidence |
DSD-0328 | Â | Â | Â | FOXL2 | development and differentiation of gonadal | NM_023067 | c.A737G | p.K246R | Missense | Het | VUS | unknown | 32,332,759 | Â | Â | Â |
DSD-0058 | Micropenis | 2 | 2 | MAP3K1 | development and differentiation of gonadal | NM_005921 | c.A1664G | p.D555G | Missense | Het | VUS | unknown | novel | Â | 0.9475 | Disease-causing with 99.9% confidence |
DSD-0058 | Â | Â | Â | FOXL2 | development and differentiation of gonadal | NM_023067 | c.G1036C | p.A346P | Missense | Het | VUS | unknown | novel | Â | Â | Â |