Table 3 Possible pathogenic variants in the genes of OI, HPP, EvC, and ATD in 3.5KJPNv2.

From: Estimation of the carrier frequencies and proportions of potential patients by detecting causative gene variants associated with autosomal recessive bone dysplasia using a whole-genome reference panel of Japanese individuals

Variation Functional category Genomic location dbSNP 3.5KJPN genotype count 3.5KJPN allele freq InterVar gnomAD ALLa gnomAD FINa gnomAD NFE Mutation database Classification Set
Position (GRCh37/hg19) RefRef Het AltAlt ClinVar HGMD
Osteogenesis imperfecta (OI)
 BMP1
 c.G1639T:p.Glu547a Stopgain chr8:22052432   3551 1 0 0.00014 P       P_interpreted 2
 c.2826 + 2 T > C Splicing chr8:22067210   3551 1 0 0.00014 P       P_interpreted 2
 c.G626T:p.Gly209Val Nonsynonymous SNV chr8:22034548   3551 1 0 0.00014 LP       LP_interpreted 2
 c.668delA:p.His223fs Frameshift deletion chr8:22034590   3551 1 0 0.00014 LP       LP_interpreted 2
 c.671delA:p.Glu224fs Frameshift deletion chr8:22034593   3551 1 0 0.00014 LP       LP_interpreted 2
 c.C831A:p.Phe277Leu Nonsynonymous SNV chr8:22035465   3551 1 0 0.00014 LP       LP_interpreted 2
 c.G850T:p.Asp284Tyr Nonsynonymous SNV chr8:22037231   3551 1 0 0.00014 LP       LP_interpreted 2
 c.A1640G:p.Glu547GLy Nonsynonymous SNV chr8:22052975 rs764357220 3551 1 0 0.00014 LP       LP_interpreted 2
 c.G1757A:p.Arg586His Nonsynonymous SNV chr8:22053092 rs755936351 3551 1 0 0.00014 LP 3.24E-05 0.0003 0    LP_interpreted 2
 c.Gly2137A:p.Gly713Ser Nonsynonymous SNV chr8:22059345 rs148687489 3551 1 0 0.00014 LP 0.0002 0 0    LP_interpreted 2
 LEPRE1
c.C1726T:p.Gln576a Stopgain chr1:43213983   3551 1 0 0.00014 P       P_interpreted 2
c.G1840Ala:p.Ala614Thr Nonsynonymous SNV chr1:43213468 rs868224632 3551 1 0 0.00014 P       LP_interpreted 2
 CRTAP
c.621 + 1 G > A Splicing chr3:33161986 rs775720622 3550 2 0 0.00028 P       P_interpreted 2
PPIB
PLOD2
 c.C1483T:p.Arg495a Stopgain chr3:145796920   3551 1 0 0.00014 P       P_interpreted 2
 c.C160T:p.Arg54a Stopgain chr3:145841966 rs780902890 3551 1 0 0.00014 P       P_interpreted 2
 SERPINH1
c.C230T:p.Ser77Leu Nonsynonymous SNV chr11:75277624   3543 9 0 0.00127 LP       LP_interpreted 2
c.G655A:p.Val219Met Nonsynonymous SNV chr11:75279808   3550 2 0 0.00028 LP       LP_interpreted 2
c.C680Thr:p.Thr227Ile Nonsynonymous SNV chr11:75279833   3551 1 0 0.00014 LP       LP_interpreted 2
c.A731T:p.Asn244Ile Nonsynonymous SNV chr11:75279993   3550 2 0 0.00028 LP       LP_interpreted 2
c.G766A:p.Val256Met Nonsynonymous SNV chr11:75280028 rs749664592 3551 1 0 0.00014 LP       LP_interpreted 2
c.G1016T:p.Arg339Leu Nonsynonymous SNV chr11:75282887 rs535510332 3551 1 0 0.00014 LP       LP_interpreted 2
c.C1046T:p.Ala349Val Nonsynonymous SNV chr11:75282917   3547 5 0 0.00070 LP       LP_interpreted 2
c.G1060Ala:p.Ala354Thr Nonsynonymous SNV chr11:75282931 rs369550626 3551 1 0 0.00014 LP 3.23E-05 0 0    LP_interpreted 2
 FKBP10
c.G1723C:p.Glu575Gln Nonsynonymous SNV chr17:39978634   3551 1 0 0.00014 LP       LP_interpreted 2
 SERPINF1
c.284-2 A > G Splicing chr17:1674321 rs113947687 3547 5 0 0.00070 P       P_interpreted 2
c.C167Gly:p.Ala56Gly Nonsynonymous SNV chr17:1673228 rs76119062 3465 86 1 0.01239 VUS 0.0004 0.0017 6.68E-05   DM p_hgmd 4
 SEC24D
c.C904T:p.Gln302a Stopgain chr4:119727007 rs770892912 3551 1 0 0.00014 P       P_interpreted 2
 WNT1                
 CREB3L1                
 SP7                
Hypophosphatasia (HPP)                
 ALPL                
 c.G407A:p.Arg136His Nonsynonymous SNV chr1:21889712 rs121918011 3550 2 0 0.00028 LP 3.23E-05 0 0 P DM LP_reported 1
 c.T979C:p.Phe327Leu Nonsynonymous SNV chr1:21900274 rs121918010 3536 16 0 0.00225 LP 9.69E-05 0 0 P DM LP_reported 1
 c.C98Gly:p.Ala33Gly Nonsynonymous SNV chr1:21887155 rs121918005 3551 1 0 0.00014 LP       LP_interpreted 2
 c.C782A:p.Pro261Gln Nonsynonymous SNV chr1:21894730 rs765149569 3550 2 0 0.00028 LP       LP_interpreted 2
 c.A1183G:p.Ile395Val Nonsynonymous SNV chr1:21902411 rs772682471 3551 1 0 0.00014 LP      DM LP_interpreted 2
 c.1559delT:p.Leu520fs Frameshift deletion chr1:21904125 rs387906525 3540 12 0 0.00169 VUS     P DM p_clinvar 3
 c.A184G:p.Met62Val Nonsynonymous SNV chr1:21887592   3551 1 0 0.00014 VUS      DM p_hgmd 4
 c.G529Ala:p.Ala177Thr Nonsynonymous SNV chr1:21890590 rs199669988 3434 116 2 0.01689 VUS 6.47E-05 0 0 VUS DM p_hgmd 4
 c.A572G:p.Glu191Gly Nonsynonymous SNV chr1:21890633   3551 1 0 0.00014 VUS      DM p_hgmd 4
 c.A1022G:p.His341Arg Nonsynonymous SNV chr1:21902250   3551 1 0 0.00014 VUS 3.23E-05 0.0003 0   DM p_hgmd 4
 c.Gly1258A:p.Gly420Ser Nonsynonymous SNV chr1:21903083   3551 1 0 0.00014 VUS      DM p_hgmd 4
 c.Gly1276A:p.Gly426Ser Nonsynonymous SNV chr1:21903101 rs770548228 3551 1 0 0.00014 VUS      DM p_hgmd 4
 c.A1307G:p.Tyr436Cys Nonsynonymous SNV chr1:21903132   3551 1 0 0.00014 VUS      DM p_hgmd 4
Ellis–van Creveld syndrome (EvC)
 EVC
c.1887-1 G > C Splicing chr4:5798748   3551 1 0 0.00014 P       P_interpreted 2
c.C884G:p.Thr295Ser Nonsynonymous SNV chr4:5747013 rs754532508 3550 2 0 0.00028 VUS 3.24E-05 0 0 VUS DM p_hgmd 4
c.C982T:p.Leu328Phe Nonsynonymous SNV chr4:5749917 rs199916502 3545 7 0 0.00099 VUS 0.0004 0 6.66E-05 Conflicting interpretations of pathogenicity DM p_hgmd 4
 EVC2
c.G2484A:p.Trp828a Stopgain chr4:5624281 rs770918273 3551 1 0 0.00014 P 3.24E-05 0 0 LP DM P_reported 1
c.C1195T:p.Arg399a Stopgain chr4:5642516 rs137852924 3550 2 0 0.00028 P 6.46E-05 0 0 P DM P_reported 1
c.1230 + 1 G > C Splicing chr4:5642240   3551 1 0 0.00014 P      DM P_interpreted 2
c.906-2 A > C Splicing chr4:5642567   3551 1 0 0.00014 P      DM P_interpreted 2
c.2536delG:p.Glu846fs Frameshift deletion chr4:5620375   3551 1 0 0.00014 LP      DM LP_interpreted 2
c.C2092T:p.Arg698a Stopgain chr4:5624673 rs781623802 3551 1 0 0.00014 LP      DM LP_interpreted 2
c.1082dupA:p.Asn361fs Frameshift insertion chr4:5664896   3551 1 0 0.00014 LP      DM LP_interpreted 2
c.C2848T:p.Arg950Trp Nonsynonymous SNV chr4:5586559 rs137852928 3551 1 0 0.00014 VUS     VUS DM p_hgmd 4
Asphyxiation thoracic dystrophy (ATD)
 DYNC2H1
c.5681_5682del:p.Glu1894fs Frameshift deletion chr11:103046970-103046971 rs767846762 3549 3 0 0.00042 P     P DM P_reported 1
c.C10045T:p.Arg3349a Stopgain chr4:103116085 rs751891969 3551 1 0 0.00014 P     P   P_reported 1
c.11277 + 1 G > A splicing chr4:103173983   3551 1 0 0.00014 P       P_interpreted 2
c.5518_5519insTA:p.Val1840fs Frameshift insertion chr4:103043994   3551 1 0 0.00014 LP       LP_interpreted 2
c.8062delA:p.Lys2688fs Frameshift deletion chr4:103070179   3551 1 0 0.00014 LP       LP_interpreted 2
c.9977delG:p.Arg3326fs Frameshift deletion chr4:103116017   3551 1 0 0.00014 LP       LP_interpreted 2
c.Cys9010T:p.Arg3004Cys Nonsynonymous SNV chr4:103091415   3548 4 0 0.00056 VUS 3.23E-05 0.0003 0   DM p_hgmd 4
 WDR34
c.1372 + 2 T > C Splicing chr9:131396503 rs758936528 3551 1 0 0.00014 P       P_interpreted 2
 IFT80                
c.C401G:p.Ser134a Stopgain chr3:160093638   3545 7 0 0.00099 P       P_interpreted 2
c.371-1 G > C Splicing chr3:160093669 rs769745055 3546 6 0 0.00085 P       P_interpreted 2
c.40-1 T > C Splicing chr3:160099511   3551 1 0 0.00014 P       P_interpreted 2
 IFT172
c.C811T:p.Arg271a Stopgain chr2:27702991   3551 1 0 0.00014 P     P   P_reported 1
c.3229-1 G > C Splicing chr2:27679521   3551 1 0 0.00014 P       P_interpreted 2
c.2116-1 G > A Splicing chr2:27684704   3551 1 0 0.00014 P       P_interpreted 2
c.571-1 G > A Splicing chr2:27704128 rs775935517 3551 1 0 0.00014 P       P_interpreted 2
c.1989delC:p.Thr663fs Frameshift deletion chr2:27685997   3551 1 0 0.00014 LP       LP_interpreted 2
 IFT140
c.C2992T:p.Gln998a Stopgain chr16:1574790   3551 1 0 0.00014 P       P_interpreted 2
c.C3214T:p.Arg1072a Stopgain chr16:1573885   3551 1 0 0.00014 LP       LP_interpreted 2
c.2767_2768del:p.Tyr923fs Frameshift deletion chr16:1575886-1575889 rs769075694 3551 1 0 0.00014 LP       LP_interpreted 2
c.G4182C:p.Thr1394Thr Synonymous SNV chr16:1568217   3551 1 0 0.00014 VUS      DM p_hgmd 4
c.C489T:p.Gly163Gly Synonymous SNV chr16:1642470 rs776597097 3551 1 0 0.00014 VUS      DM p_hgmd 4
 WDR19
c.634dupT:p.Leu211fs Frameshift insertion chr4:39206803 rs587777348 3550 2 0 0.00028 P     P DM P_reported 1
c.2165 + 1 G > T Splicing chr4:39246173   3551 1 0 0.00014 P      DM P_interpreted 2
c.2782-2 A > G Splicing chr4:39269613 rs753291151 3550 2 0 0.00028 P       P_interpreted 2
c.Gly2365C:p.Gly789Arg Nonsynonymous SNV chr4:39241898   3551 1 0 0.00014 LP       LP_interpreted 2
 TTC21B
c.G1111T:p.Glu371a Stopgain chr2:166786234   3551 1 0 0.00014 P       P_interpreted 2
c.430-2 A > C Splicing chr2:166799853   3551 1 0 0.00014 P       P_interpreted 2
c.3845_3846del:p.Tyr1282fs Frameshift deletion chr2:166732702-166732703   3551 1 0 0.00014 LP       LP_interpreted 2
c.3224_3225insGAAACTGT:p.Val1075fs Frameshift insertion chr2:166747027   3550 2 0 0.00028 LP       LP_interpreted 2
c.Cys2599T:p.Arg867Cys Nonsynonymous SNV chr2:166758390 rs746700857 3551 1 0 0.00014 VUS 3.24E-05 0 0   DM p_hgmd 4
c.A1697G:p.His566Arg Nonsynonymous SNV chr2:166773969 rs146320075 3551 1 0 0.00014 VUS 0.0014 0.0023 0.0021 VUS DM p_hgmd 4
  1. B benign, DM disease-causing mutation, FIN Finnish, gnomAD gnomAD the Genome Aggregation Database (https://gnomad.broadinstitute.org/), LB likely benign, LP likely pathogenic, NFE non-Finnish European, P pathogenic, VUS variant of significant.
  2. aSee “Materials and Methods” and Fig. 1.