Table 1.
Mutational spectrum of 11 subjects from 10 families with DFNB9
| Family ID | Variant (OTOF) NM_001287489 NP_001274418 |
State | Prediction algorithm | Conservation score | MAF | Classification of pathogenic variants [31] | References | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mutation taster | PolyPhen-2 | SIFT | PhyloP | GERP++ | Global MAF | KRGDB (n = 1722) | |||||
| SB10-23 | c.5816G > A: p.Arg1939Gln rs201326023 |
Hom | DC | PD | D | 2.261 | 2.28 | T = 0.00003/1 (ExAC) T = 0.0002/1 (1000 Genomes) |
T = 0.001452/5 | Pathogenic (PS4, PM2, PM3 PP1, PP3, PP4) |
[31] |
| SH132-273 | c.5816G > A: p.Arg1939Gln rs201326023 |
Hom | DC | PD | D | 2.261 | 2.28 | T = 0.00003/1 (ExAC) T = 0.0002/1 (1000 Genomes) |
T = 0.001452/5 | Pathogenic | [31] |
| SB22-51 | c.5816G > A: p.Arg1939Gln rs201326023 |
Het | DC | PD | D | 2.261 | 2.28 | T = 0.00003/1 (ExAC) T = 0.0002/1 (1000 Genomes) |
T = 0.001452/5 | Pathogenic | [31] |
| Large genomic deletion Chr2:26710657 ~ 26706557 | Het | NA | NA | NA | NA | NA | Pathogenic (PVS1, PP1, PP4) | [16] | |||
| SB204-398 | c.5816G > A: p.Arg1939Gln rs201326023 |
Het | DC | PD | D | 2.261 | 2.28 | T = 0.00003/1 (ExAC) T = 0.0002/1 (1000 Genomes) |
T = 0.001452/5 | Pathogenic | [31] |
| c.5566C > T: p.Arg1856Trp rs368155547 |
Het | DC | PD | D | 2.963 | 2.84 | A = 0.00004/5 (ExAC) A = 0.00008/1 (GO-ESP) |
A = 0.000871/3 | Pathogenic (PS4, PM2, PM3 PP1, PP3, PP4) |
[10] | |
| SH81-185 | c.5816G > A: p.Arg1939Gln rs201326023 |
Het | DC | PD | D | 2.261 | 2.28 | T = 0.00003/1 (ExAC) T = 0.0002/1 (1000 Genomes) |
T = 0.001452/5 | Pathogenic | [31] |
| c.2521G > A: p.Glu841Lys rs772729658 |
Het | DC | PD | D | 5.523 | 5 | T = 0.00003/3 (ExAC) | ND | Pathogenic (PS4, PM2, PM3 PP1, PP3, PP4) |
[16] | |
| SB239-465 | c.5816G > A: p.Arg1939Gln rs201326023 |
Het | DC | PD | D | 2.261 | 2.28 | T = 0.00003/1 (ExAC) T = 0.0002/1 (1000 Genomes) |
T = 0.001452/5 | Pathogenic | [31] |
| c.3032T > C: p.Leu1011Pro rs80356596 |
Het | DC | PD | D | 5.012 | 4.64 | ND | ND | Pathogenic (PS4, PM2, PM3 PP1, PP3, PP4) |
[32] | |
| SB239-466 | ac.5791C > A: p.Pro1931Thr rs537706054 | Het | DC | PD | D | 5.867 | 5.22 | T = 0.000008/1 (ExAC) | ND | Pathogenic (PM2, PM3, PP1, PP3, PP4) |
This study |
| c.2521G > A: p.Glu841Lys rs772729658 |
Het | DC | PD | D | 5.523 | 5 | T = 0.00003/3 (ExAC) | ND | Pathogenic | [16] | |
| SH195-443 | c.3192C > G: p.Tyr1064Ter rs766819324 |
Hom | DC | NA | NA | 1.937 | 2.78 | C = 0.000008/1 (ExAC) | C = 0.00029/1 | Pathogenic (PVS1, PM2, PP1, PP3, PP4) | [15] |
| SH234-547 | c.5816G > A: p.Arg1939Gln rs201326023 |
Het | DC | PD | D | 2.261 | 2.28 | T = 0.00003/1 (ExAC) T = 0.0002/1 (1000 Genomes) |
T = 0.001452/5 | Pathogenic | [31] |
| c.5566C > T: p.Arg1856Trp rs368155547 |
Het | DC | PD | D | 2.963 | 2.84 | A = 0.00004/5 (ExAC) A = 0.00008/1 (GO-ESP) |
A = 0.000871/3 | Pathogenic | [10] | |
| AJ2-3 |
ac.5534G > A: p.Gly1845Glu dbSNP ID:ND |
Het | DC | PD | D | 5.739 | 4.97 | ND | ND | Pathogenic (PM2, PM3 PP1, PP3, PP4) |
This study |
| c.3032T > C: p.Leu1011Pro rs80356596 |
Het | DC | PD | D | 5.012 | 4.64 | ND | ND | Pathogenic | [32] | |
| SH230-538 | c.2521G > A: p.Glu841Lys rs772729658 |
Het | DC | PD | D | 5.523 | 5 | T = 0.00003/3 (ExAC) | ND | Pathogenic | [16] |
|
ac.4227 + 5G > C rs571671530 |
Het | DC | NA | NA | 1.616 | 3.95 | G = 0.00006/7 (ExAC) G = 0.0002/1 (1000 Genomes) |
ND | Likely pathogenic (PM2, PM3 PP1, PP3, PP4) |
This study | |
Splice site variant prediction tools by ESEfinder, NNSplice, and NetGene2: splice site broken. Normal score (10.34940) and mutant score (6.54650) by ESEfinder, Normal score (0.99) and mutant score (0.50) by NNSplice, Normal score (0.997) and mutant score (0.685) by NetGene2
In silico prediction Algorithm: Polyphen-2 (http://genetics.bwh.harvard.edu/pph2/index.shtml); SIFT (http://sift.jcvi.org/www/SIFT_chr_coords_submit.html) or SIFT-indels2 (http://sift.bii.a-star.edu.sg/www/SIFT_indels2.html)
Conservation tools: GERP++ score in the UCSC Genome Browser (http://genome-asia.ucsc.edu/); PhyloP score from the Mutation Taster (http://www.mutationtaster.org/)
Splice site prediction tools: ESEfinder (http://rulai.cshl.edu/cgi-bin/tools/ESE3/esefinder.cgi?process=home); NNSplice (http://www.fruitfly.org/seq_tools/splice.html); NetGene2 (http://www.cbs.dtu.dk/services/NetGene2/)
ExAC, Exome Aggregation Consortium (http://exac.broadinstitute.org/)
1000 Genomes (https://www.ncbi.nlm.nih.gov/variation/tools/1000genomes/)
KRGDB, Korean Reference Genome DB (http://152.99.75.168/KRGDB/)
Het, heterozygote mutant; Hom, homozygote mutant; DC, disease causing; PD, probably damaging; D, damaging; ND, not detected; NA, not applicable
aNovel variant