Table 3.
Candidate variants identified by targeted NGS and bioinformatics analysis
| Samples | Gene_RefSeq_muation | Het/Hom | Depth | Freq_1KG | Freq_ExAC | PoPh-2 | SIFT | MuTa | Origin | ACMG Classification |
|---|---|---|---|---|---|---|---|---|---|---|
| FS0005 | SALL4:NM_020436.4: c.1252C>T, (p.R418C) | het | 106:78 | / | 8.25E-06 | PRD | T | DC | NA | / |
| FS0011 | COL4A6:NM_001847.3: c.2852G>A, (p.G951E) | het | 296:298 | / | / | PRD | D | DC | NA | / |
| FS0018 | ERCC6:NM_000124.3: c.1769C>T, (p.P590L) | het | 580:329 | / | / | PRD | D | DC | Pat | PM1 PM2 PP3 PP4 (LP) |
| FS0028 | DNAH6:NM_001370.1: c.11689G>A, (p.V3897I) | het | 447:468 | / | 8.91E-05 | PRD | D | DC | NA | / |
| FS0032 | MSH5:NM_025259.5: c.604G>C, (p.G202R) | het | 256:309 | / | / | PRD | D | NA | Pat/Mat* | PM2 PM3 PP2 PP3 PP4 (LP) |
| MSH5:NM_025259.5: c.2063T>C, (p.I688T) | het | 745:779 | / | 1.68E-05 | POD | D | NA | Pat/Mat* | PM1 PM2 PP2 PP3 PP4 (LP) | |
| FS0033 | DNAH6:NM_001370.1: c.5045C>G, (p.P1682R) | het | 252:195 | / | / | PRD | D | DC | NA | / |
| FS0048 | AMHR2:NM_020547.3: c.56C>G, (p.P19R) | het | 302:268 | / | / | PRD | T | DC | NA | / |
| FS0054 | MCM9:NM_017696.2: c.1291A>G, (p.M431V) | het | 223:225 | / | / | PRD | D | DC | Mat | PM1 PM2 PM3 PP4 (LP) |
| MCM9:NM_017696.2: c.1157C>T, (p.T386M) | het | 126:121 | / | / | PRD | D | DC | Pat | PM1 PM2 PM3 PP4 (LP) | |
| FS0066 | DNAH6:NM_001370.1: c.8104A>G, (p.T2702A) | het | 501:536 | / | / | POD | D | DC | NA | / |
| FS0074 | DNAH6:NM_001370.1: c.10942A>G, (p.N3648D) | het | 79:67 | / | / | POD | T | DC | NA | / |
| FS0084 | POLG:NM_002693.2: c.2832G>C, (p.E944D) | het | 1102:1041 | / | / | PRD | T | DC | NA | PM1 PM2 PP3 PP4 (LP) |
| FS0099 | GDF9:NM_005260.5: c.238C>T, (p.Q80X) | hom | 3:818 | / | 8.0E-06 | NA | D | DC | NA | PVS1 PM2 PM3 PP3 PP4 (P) |
| FS0100 | COL4A6:NM_001847.3: c.2653G>A, (p.G885R) | het | 708:703 | / | / | PRD | D | DC | NA | / |
| FS0107 | CYP17A1:NM_000102.3: c.1459_1467del, (p.487_489del) | het | 328:321 | / | 1.291E-05 | NA | NA | DC | Mat | PS3 PM2 PM3 PM4 PP1 PP3 PP4 (P) |
| CYP17A1:NM_000102.3: c.985_987delinsAA, (p.Y329fs) | het | 259:271 | / | 4.947E-05 | NA | NA | DC | Pat | PVS1 PS3 PM2 PM3 PP1 PP3 PP4 (P) | |
| FS0117 | CLPP:NM_006012.2: c.355A>C, (p.I119L) | het | 301:248 | / | / | PRD | D | DC | Not Mat# | PM1 PM2 PP3 PP4 (LP) |
| CLPP:NM_006012.2: c.688A>C, (p.M230L) | het | 177:179 | / | / | BN | T | DC | Mat# | PM1 PM2 PM3 PP4 (LP) | |
| M2070 | FOXL2:NM_023067.3: c.273C>A, (p.Y91X) | het | 36:27 | / | 2.0E-05 | NA | D | DC | NA | PVS1 PS1 PM2 PM4 PM6 PP3 PP4 (P) |
| FS0133 | SALL4:NM_020436.4: c.541G>A, (p.V181M) | Het | 336:180 | / | 4.0E-04 | PRD | D | DC | Not Mat | / |
| FS0134 | EIF2B2:NM_014239.3: c.254T>A, (p.V85E) | Hom | 10:2319 | / | 8.276E-05 | PRD | D | DC | Mat&Pat | PS1 PS3 PM2 PP3 PP4 PP5 (P) |
| FS0140 | POLG:NM_002693.2: c.2821A>G, (p.I941V) | Het | 1145:1123 | / | / | PRD | D | DC | NA | PM1 PM2 PP3 PP4 (LP) |
| FS0158 | FOXL2:NM_023067.3: c.804dupC, (p.G269fs) | Het | 44:50 | / | / | NA | NA | DC | De novo | PVS1 PS1 PS2 PM2 PM4 PP3 PP4 (P) |
All the variants were validated by Sanger sequencing. Het heterozygosity, Hom homozygosity, Freq_1KG frequency data of East Asians from the 1000. Genomes Database (http://www.internationalgenome.org/); ExAC the Exome Aggregation Consortium (http://exac.broadinstitute.org/); “/” indicates no records. PoPh-2 PolyPhen-2 variant prediction software, PRD probable damaging, POD possibly damaging, BN benign. SIFT SIFT variant prediction software, T tolerated, D damaging. MuTa Mutation Taster variant prediction software, DC disease causing. Origin obtained by direct sequencing parents’ samples, Mat maternal origin, Pat paternal origin, NA not available. ACMG Classification standards and guidelines for the interpretation of sequence variants by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, P pathogenic, LP likely pathogenic
*c.604G>C and c.2063T>C of MSH5 in FS0032 were compound heterozygous confirmed by 10× Genomics, predicted to be biparental origin
#c.355A>C and c.688A>C of CLPP in FS0117 were compound heterozygous confirmed by nanopore sequencing