Table 1
TOR2A (GRCh38/hg38, NC_000009.12) primers for Sanger sequencing.
| PRIMER NAME | SEQUENCE (5’ → 3’) | LOCUS | PRODUCT SIZE (bp) |
|---|---|---|---|
| TOR2A_5’UTR-F | CCT GAG CCT TCT TAC TGT GAA T | NC_000009.12: 127731790–769 | 306 |
| TOR2A-5’UTR-R | GCC TCC TTC CAG AGC AAT TA | NC_000009.12: 127731505–485 | |
| TOR2A-E1F | AGGAGCGTCGGGAGTTGTAG | NC_000009.12: 127735387–367 | 378 |
| TOR2A-E1R | CTGGGTCCTCAGCTTCTCTG | NC_000009.12:127735032–010 | |
| TOR2A-E2F | CCAGACCAGGTTCCAGACAT | NC_000009.12: 127734646–626 | 391 |
| TOR2A-E2R | CACCCCATGGTGAGAACAG | NC_000009.12: 127734275–256 | |
| TOR2A-E3F | TTGGGAAGAGGTCTGGTGTT | NC_000009.12: 127733627–607 | 300 |
| TOR2A-E3R | AGCTGAACCTCTGAGAAGTGG | NC_000009.12: 127733349–328 | |
| TOR2A-E4F | AGCGTTTTCAGTGGAGTTGG | NC_000009.12: 127732827–807 | 398 |
| TOR2A-E4R | AGTCACAAAGCTGGGAGTGC | NC_000009.12: 127732847–827 | |
| TOR2A-E5F | TCTCCCCTCTTGTGAAGCAC | NC_000009.12: 127732329–309 | 397 |
| TOR2A-E5R | TCCGTTCATCTCACTTGGTG | NC_000009.12: 127731953–933 | |
| TOR2A-3’UTR-F | AGC ACT AAT GGC ACA GAG TAA G | NC_000009.12: 127735703–681 | 345 |
| TOR2A-3’UTR-R | GCC CAT CGC CTA CAA CTC | NC_000009.12: 127735377–359 |
Table 2
TOR2A (GRCh38/hg38, NC_000009.12, NM_001085347.2) variants identified with Sanger sequencing.
| VARIANT | NUMBER OF SUBJECTS | ALLELE FREQUENCY | HOMOZYGOTES | PROTEIN | GNOMAD V3.1.2 ALLELE FREQUENCY | CADDPHRED-SCALED | REVEL | MetaLR |
|---|---|---|---|---|---|---|---|---|
| NM_001085347.3:c.593+31G>C NM_130459.4:c.624G>C (rs564754) | 234/307 (76.2%) | 350/614 (57.0%) | 58 | NA p.Trp208Cys | 97582/152038 (64.18%) | 0.203 | 0.032 | 0 |
| NM_001085347.3: c.721+32A>G (rs515182) | 290/307 (94.5%) | 370/614 (60.3%) | 40 | NA | 101903/152022 (67.03%) | 4.89 | NA | NA |
| NM_001085347.3: c.607A>G (rs538066) | 260/307 (84.7%) | 560/614 (91.2%) | 150 | p. Lys203Glu | 150579 /152218 (98.92%) | 20.4 | 0.091 | 0 |
| NM_001085347.3:c.793C>T (rs114990094) | 10/307 (3.25%) | 12/614 (1.95%) | 0 | p. Arg265Trp | 3076/152220 (2.02%) | 26.0 | 0.291 | 0.164 |
Table 3
TOR2A variants reported by NCBI’s ClinVar and PubMed.
| VARIANT(ACCESSION) | PROTEIN CHANGE | CONDITION (NUMBER OF PROBANDS) | CLINICAL SIGNIFICANCE | gnomAD V3.1.2 (ALLELE FREQUENCY) | CADDPHRED-SCALED | MetaLR | REVEL | REF. |
|---|---|---|---|---|---|---|---|---|
| c.194T>C (SCV003669886.1) | p. Leu65Pro | Inborn genetic disease (N = 1) | Uncertain significance | – | 31.0 | 0.2864 | 0.664 | [14] |
| c.247C>T (SCV003546031.1) | p. Pro83Ser | Inborn genetic disease (N = 1) | Uncertain significance | 2/152200 | 28.3 | 0.2573 | 0.376 | |
| c.338G>A (SCV003885945.1) | p. Gly113Asp | Inborn genetic disease (N = 1) | Uncertain significance | – | 31.0 | 0.02109 | 0.024 | |
| c.423T>A (SCV003950745.1) | p. Asp141Glu | Inborn genetic disease (N = 1) | Uncertain significance | 2/152214 | 16.1 | 0.04569 | 0.031 | |
| c.463C>T (SCV003757814.1) | p. Arg155Cys | Inborn genetic disease (N = 1) | Uncertain significance | 2/152230 | 24.5 | 0.3835 | 0.281 | |
| c.553T>C (SCV003661212.1) | p. Tyr185His | Inborn genetic disease (N = 1) | Uncertain significance | – | 23.5 | 0.0976 | 0.182 | |
| c.62T>C (SCV003534402.1) | p.Val21Ala | Inborn genetic disease (N = 1) | Uncertain significance | 3/152194 | 14.8 | 0.1089 | 0.0540 | |
| c.734A>G (SCV003566928.1) | p.Asn245Ser | Inborn genetic disease (N = 1) | Uncertain significance | 1/231144 | 7.8 | 0.0521 | 0.040 | |
| c.737C>T (SCV003615110.1) | p.Ser246Leu | Inborn genetic disease (N = 1) | Uncertain significance | 2/152226 | 26.0 | 0.4321 | 0.563 | |
| c.766G>A (SCV004004774.1) | p. Ala256Thr | Inborn genetic disease (N = 1) | Uncertain significance | 6/276576 | 21.2 | 0.1399 | 0.089 | |
| c.785C>G (SCV003708033.1) | p. Pro262Arg | Inborn genetic disease (N = 1) | Uncertain significance | 4/152198 | 27.3 | 0.5009 | 0.809 | |
| c.805C>T (SCV003951769.1) | p. Arg269Trp | Inborn genetic disease (N = 1) | Uncertain significance | 7/279546 | 26.5 | 0.3993 | 0.172 | |
| c.907C>A (SCV001041175.1) | p. Gln303Lys | Inborn genetic disease (N = 1) | Uncertain significance | 67/152230 | 17.1 | 0.0676 | 0.146 | |
| c.925G>A (SCV003551979.1) | p. Gly309Ser | Inborn genetic disease (N = 1) | Uncertain significance | 9/152230 | 27.1 | 0.5849 | 0.813 | |
| c.937G>A (SCV003529445.1) | p. Val313Met | Inborn genetic disease (N = 1) | Uncertain significance | 6/152246 | 25.4 | 0.5539 | 0.658 | |
| c.568C>T (NM_001085347.3) | p.Arg190Cys | BSP/BSP+ (N = 3, one pedigree) | Likely pathogenic | 5/152188 | 29.2 | 0.548 | 0.5 | [11] |
| c.593+31G>C (NM_001085347.2) | p. Trp208Cys | BSP | Benign | 97582/ 152038 | 0.203 | 0.000 | 0.0320 | [13] |
| c.-42G>A (NM_130459.3) | NA | BSP/BSP+ (N = 6) | Benign | 12139/152166 | 12.2 | – | – | [12] |
| c.277_288dup (NM_001085347.3) | p.Gly93_Gly96dup | BSP/BSP+ (N = 1 homozygote) | Uncertain significance | 11/152226 | 21.5 | – | – | |
| c.418–51T>G (NM_001085347.3) | NA | BSP/BSP+ (N = 35), Controls (N = 40) | Benign | 98659/151956 | 10.3 | – | – | |
| c.555C>T (NM_001085347.3) | p.Tyr185= | BSP/BSP+ (N = 1), Controls (N = 0) | Uncertain significance | 9/152204 | 0.382 | – | – | |
| c.593+36del (NM_001085347.3) c.629del (NM_130459.4) | NA p.Gly210AlafsTer60 | BSP/BSP+ (N = 1), Controls (N = 0) | Uncertain significance | 3/152204 | 0.81 | – | – | |
| c.594–46C>T (NM_001085347.3) | NA | BSP/BSP+ (N=23 heterozygotes, 6 homozygotes), Controls (18 heterozygotes, 8 homozygotes) | Benign | 18456/152198 | 0.252 | – | – | |
| c.721+32A>G (NM_001085347.3) | NA | BSP/BSP+ (N=35 heterozygotes, 9 homozygotes), Controls (48 heterozygotes, 24 homozygotes) | Benign | 101903/152022 | 4.89 | – | – | |
| c.721+52G>A (NM_001085347.3) | NA | BSP/BSP+ (N = 10), Controls (N = 12) | Benign | 25185/152088 | 7.55 | – | – | |
| c.594–59C>T (NM_001085347.3) | NA | BSP/BSP+ (N = 1), Controls (N = 0) | Uncertain significance | 7/152224 | 0.154 | – | – | |
| c.721+83C>T (NM_001085347.3) | NA | BSP/BSP+ (N = 1), Controls (N = 0) | Uncertain significance | – | 1.89 | – | – | |
| c.594-55C>A (NM_001085347.3) | NA | BSP/BSP+ (N = 1), Controls (N = 0) | Uncertain significance | 28/152228 | 6.55 | – | – | |
| c.*28del (NM_001085347.3) | NA | BSP/BSP+ (N = 9), Controls (N = 8) | Benign | 387/152220 | 0.128 | – | – | |
| c.*125A>G (NM_001085347.3) | N/A | BSP/BSP+ (N = 1), Controls (N = 1) | Uncertain significance | 1/152222 | 5.65 | NA | NA | |
| c.786G>A (NM_001085347.3) | p.Pro262= | BSP/BSP+ (N = 1), Controls (N = 1) | Benign | 83/152120 | 0.572 | 0.0614 | 0.0440 |