TABLE 1.
Alterations in 10 Target Genes Among Kenyan Wilms Tumors
| Chromo- some |
REF | Alteration | Location | Function | Gene | Amino acid change | Tumor | Cosmic68 | esp- 6500si |
SIFT | Polyphen 2_HVAR |
LRT | Mutation taster |
MutatioN/ assessor |
FATHMM | Radial SVM |
LR | Cadd gt10 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | G | A | exonic | nonsynonym | CRABP2 | NM_001878:exon2:c.C178T:p.R60C | KWT-39 | COSM98340 | N/A | B | B | D | D | M | T | T | T | 15.34 |
| 2 | G | A | exonic | nonsynonym | SIX2 | NM_016932:exon1:c.C29T:p.T10M | KWT-10 | N/A | N/A | D | P | U | D | M | D | D | D | 25.5 |
| 2 | C | T | exonic | nonsynonym | MYCN | NM_005378:exon2:c.C131T:p.P44L | KWT-22, 38 | COSM35624 | N/A | D | D | N | D | M | T | T | T | 27.3 |
| 2 | C | T | exonic | nonsynonym | MYCN | NM_005378:exon2:c.C220T:p.P74S | KWT-21, 30 | N/A | N/A | P | P | N | D | L | T | T | T | N/A |
| 2 | C | T | exonic | nonsynonym | MYCN | NM_005378:exon2:c.C173T:p.T58M | KWT-26 | N/A | N/A | D | D | N | D | M | T | T | T | 23.1 |
| 2 | G | A | exonic | nonsynonym | MYCN | NM_005378:exon2:c.G191A:p.S64N | KWT-29 | N/A | N/A | D | D | D | D | M | T | T | T | 21 |
| 2 | A | C | exonic | nonsynonym | MYCN | NM_005378:exon3:c.A1111C:p.S371R | KWT-43, 44 | N/A | N/A | B | B | N | D | M | T | T | T | 16.62 |
| 3 | A | G | exonic | nonsynonym | CTNNB1 | NM_001098209:exon3:c.A121G:p.T41A | KWT-16 | COSM5664 | N/A | P | P | D | D | M | T | T | T | 23.7 |
| 3 | T | C | exonic | nonsynonym | CTNNB1 | NM_001098209:exon3:c.T133C:p.S45P | KWT-5, 27 | COSM5663 | N/A | D | P | D | D | M | T | T | T | 23.6 |
| 3 | C | T | exonic | nonsynonym | CTNNB1 | NM_001098209:exon3:c.C134T:p.S45F | KWT-17 | COSM5667 | N/A | D | D | D | D | M | T | T | T | 24.8 |
| 3 | G | A | exonic | nonsynonym | CTNNB1 | NM_001098209:exon4:c.G439A:p.E147K | KWT-30 | N/A | N/A | P | P | D | D | M | T | T | T | 23.8 |
| 3 | A | T | exonic | nonsynonym | CTNNB1 | NM_001098209:exon6:c.A801T:p.E267D | KWT-13, 39 | N/A | N/A | B | B | D | D | N | T | T | T | 10.11 |
| 3 | G | A | exonic | nonsynonym | CTNNB1 | NM_001098209:exon7:c.G955A:p.G319S | KWT-4, 26 | N/A | N/A | B | B | D | D | L | T | T | T | 20.6 |
| 3 | C | G | exonic | nonsynonym | CTNNB1 | NM_001098209:exon7:c.C1006G:p.L336V | KWT-9 | N/A | N/A | D | P | D | D | M | T | T | T | 22.8 |
| 11 | G | A | exonic | nonsynonym | WT1 | NM_000378:exon1:c.C34T:p.P12S | KWT-9* | N/A | N/A | B | B | N/A | D | N | T | T | T | 18.07 |
| 11 | C | T | exonic | nonsynonym | WT1 | NM_000378:exon1:c.G37A:p.A13T | KWT-25 | N/A | N/A | P | B | N/A | D | N | T | T | T | 21 |
| 11 | GC | G | exonic | frameshift | WT1 | NM_000378:exon1:c.520delG:p.A174fs | KWT-17* | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| 11 | G | T | exonic | nonsynonym | WT1 | NM_000378:exon2:c.C719A:p.P240H | KWT-29 | N/A | N/A | P | P | U | D | L | D | D | D | 28.6 |
| 11 | G | A | exonic | nonsynonym | IGF2 | NM_001042376:exon3:c.C319T:p.R107W | KWT-8 | N/A | N/A | D | P | U | N | L | D | D | D | 14.03 |
| 11 | G | A | exonic | nonsynonym | IGF2 | NM_000612:exon4:c.C317T:p.P106L | KWT-30 | N/A | N/A | D | P | U | D | M | D | D | D | 16.73 |
| 11 | G | A | exonic | nonsynonym | IGF2 | NM_000612:exon4:c.C515T:p.P172L | KWT-3 | N/A | N/A | B | B | U | N | N | D | T | T | 11.4 |
| 17 | G | T | exonic | nonsynonym | TP53 | NM_001126115:exon1:c.C56A:p.P19H | KWT-33 | COSM259150; 259151; 259152; 259149; 11476 | N/A | D | D | D | D | M | D | D | D | 16.15 |
| 17 | C | T | exonic | nonsynonym | TP53 | NM_001126115:exon1:c.G128A:p.R43H | KWT-12 | COSM10648; 99022; 1640851; 99024; 99023; 99914 | N/A | D | D | D | A | M | D | D | D | 31 |
| 17 | G | A | exonic | nonsynonym | TP53 | NM_001126118:exon3:c.C22T:p.P8S | KWT-18 | N/A | 0.0052 | B | B | N | N | L | D | D | D | N/A |
| 17 | G | C | exonic | nonsynonym | TP53 | NM_001126118:exon3:c.C56G:p.P19R | KWT-19 | N/A | 0.0004 | D | B | N | N | N | D | D | D | N/A |
| 17 | C | T | exonic | nonsynonym | TP53 | NM_001126115:exon3:c.G337A:p.G113S | KWT-10 | COSM1640833; 121037; 121035; 6932; 121036 | 0.0001 | D | D | D | D | M | D | D | D | 33 |
| 17 | G | A | exonic | nonsynonym | TP53 | NM_001126115:exon7:c.C734T:p.T245I | KWT-3, 18 | N/A | N/A | B | B | N | D | M | D | D | D | 14.92 |
| 17 | G | A | exonic | nonsynonym | TP53 | NM_001126115:exon7:c.C737T:p.S246F | KWT-13 | N/A | N/A | D | P | N | D | M | D | D | D | 22 |
| 17 | G | A | exonic | nonsynonym | TP53 | NM_001126115:exon7:c.C739T:p.R247C | KWT-8, 40 | N/A | N/A | B | B | N | D | L | D | D | D | 12.79 |
| 17 | C | T | exonic | nonsynonym | TP53 | NM_001126115:exon7:c.G740A:p.R247H | KWT-13, 23 | COSM44189 | N/A | B | B | N | N | L | D | D | D | 13.21 |
| 17 | C | G | exonic | nonsynonym | TP53 | NM_001126115:exon7:c.G740C:p.R247P | KWT-1, 13, 23 | N/A | N/A | B | B | N | D | L | D | D | D | 12.75 |
| 17 | G | A | exonic | nonsynonym | TP53 | NM_001126115:exon7:c.C742T:p.H248Y | KWT-23 | N/A | N/A | P | B | N | D | M | D | D | D | 13.43 |
| 17 | C | T | exonic | nonsynonym | TOP2A | NM_001067:exon6:c.G497A:p.G166E | KWT-1 | N/A | N/A | D | D | D | D | H | D | D | D | 28.2 |
| 17 | C | T | exonic | nonsynonym | TOP2A | NM_001067:exon6:c.G521A:p.S174N | KWT-1 | N/A | N/A | D | D | D | D | H | T | D | D | 32 |
| 17 | G | A | exonic | nonsynonym | TOP2A | NM_001067:exon9:c.C989T:p.A330V | KWT-1 | N/A | N/A | B | B | N | D | N | T | T | T | N/A |
| 17 | C | T | exonic | nonsynonym | TOP2A | NM_001067:exon12:c.G1444A:p.G482R | KWT-30 | N/A | N/A | D | D | D | D | H | T | T | T | 33 |
| 17 | C | T | exonic | nonsynonym | TOP2A | NM_001067:exon19:c.G2279A:p.G760D | KWT-27 | N/A | N/A | D | D | D | D | H | T | D | D | 32 |
| 17 | A | C | exonic | nonsynonym | TOP2A | NM_001067:exon21:c.T2518G:p.W840G | KWT-41 | N/A | N/A | D | D | D | D | M | T | T | T | 19.42 |
| 17 | A | G | exonic | nonsynonym | TOP2A | NM_001067:exon21:c.T2525C:p.I842T | KWT-30 | N/A | N/A | B | B | D | D | L | T | T | T | 14.54 |
| 17 | C | T | exonic | nonsynonym | TOP2A | NM_001067:exon25:c.G3214A:p.E1072K | KWT-1 | N/A | N/A | P | P | D | D | M | T | T | T | 33 |
| X | G | C | exonic | stopgain | AMER1 | NM_152424:exon2:c.C125G:p.S42X | KWT-40 | N/A | N/A | N/A | N/A | N | A | N/A | N/A | N/A | N/A | 21.7 |
| X | G | A | exonic | stopgain | AMER1 | NM_152424:exon2:c.C1072T:p.R358X | KWT-1 | COSM 193868, 22960 | N/A | N/A | N/A | D | A | N/A | N/A | N/A | N/A | 38 |
| X | C | A | exonic | nonsynonym | AMER1 | NM_152424:exon2:c.G2014T:p.G672W | KWT-44 | N/A | N/A | D | D | N | D | L | T | T | T | N/A |
| X | C | T | exonic | nonsynonym | AMER1 | NM_152424:exon2:c.G2440A:p.V814M | KWT-30 (F) | N/A | N/A | D | P | N/A | D | N | T | T | T | 14.9 |
| X | G | A | exonic | nonsynonym | AMER1 | NM_152424:exon2:c.C2510T:p.S837F | KWT-14 | N/A | N/A | D | D | N/A | D | N | T | T | T | 16.45 |
| X | T | G | exonic | nonsynonym | AMER1 | NM_152424:exon2:c.A2543C:p.K848T | KWT-14 | N/A | N/A | D | D | N/A | D | N | T | T | T | 12.42 |
| X | G | A | exonic | nonsynonym | AMER1 | NM_152424:exon2:c.C2545T:p.H849Y | KWT-14 | N/A | N/A | P | B | N/A | D | N | T | T | T | N/A |
| X | C | T | exonic | nonsynonym | CITED1 | NM_001144886:exon3:c.G124A:p.V42M | KWT-30 (F) | N/A | N/A | D | P | N | N | L | T | T | T | 18.79 |
nonsynonym = nonsynonymous alteration
*
Wilms tumor specimens having combined mutations in WT1 and CTNNB1.
(F) designates a female patient for the X-chromosome genes, AMER1 and C1TED1, only.
| Score (dbtype) | Categorical Prediction |
| SIFT (sift) | D: Deleterious (sift<=0.05); T: tolerated (sift>0.05) |
| PolyPhen 2 HDIV (pp2_hdiv) | D: Probably damaging (>=0.957), P:possibly damaging (0.453<=pp2_hdiv<=0.956); B:benign (pp2_hdiv<=0.452) |
| PolyPhen 2 HVar (pp2_hvar) | D: Probably damaging (>=0.909), P:possibly damaging (0.447<=pp2_hdiv<=0.909); B:benign (pp2_hdiv<=0.446) |
| LRT (lrt) | D: Deleterious; N: Neutral; U: Unknown |
| MutationTaster (mt) | A” (“disease-causing-automatic”); “D” (“disease-causing”); “N” (“polymorphism”); “P” (“polymorphism-automatic”) |
| MutationAssessor (ma) | H: high; M: medium; L: low; N: neutral. H/M means functional and L/N means non-functional |
| FATHMM (fathmm) | D: Deleterious; T: Tolerated |
| MetaSVM (metasvm) | D: Deleterious; T: Tolerated |
| MetaLR (metalr) | D: Deleterious; T: Tolerated |
| CADD | Combined Annotation Dependent Depletion |