Table 2.
Novel variants and candidate genes 1 for hearing loss and temporal bone anomalies.
| ID | Gene | Variant | rsID | gnomAD | GenomeAsia 100k SEA 2 | Scaled CADD | Damaging Results from dbNSFP Tools |
|---|---|---|---|---|---|---|---|
| 1 | DSPP | NM_014208: c.730G>A (p.(Gly244Arg)) | 1044690454 | NA | 0.0014 | 24.3 | FA,mLR,mSVM, MT,PP2,SI |
| 3 | LMX1A | NM_177398: c.606G>C (p.(Leu202Phe)) | NA | NA | NA | 24.8 | FA,LRT,mLR, mSVM,MT,PP2, PR,SI |
| 5 | DMXL2 | NM_015263: c.257T>C (p.(Leu86Ser)) | 761692429 | OTH: 0.0005 | NA | 24.1 | LRT,MT,PP2,SI |
| 6 | PTPRQ | NM_001145026: c.6179T>C (p.(Val2060Ala)) | 375150180 | EAS: 0.00097 | 0.017 | 27.8 | MT,SI |
| 7 | PCDH15/CDH23 | NM_001354411: c.3787C>T (p.(Pro1263Ser)); NM_022124: c.3262G>A (p.(Val1088Met)) | 775954124; 200632520 | EAS: 0.004; EAS: 0.002 | NA; 0.003 | 24.9; 24.3 | MA,MT,PP2,PR, SI; LRT,MA,mLR, mSVM,MT,PP2,SI |
| 23 | CDH23 | NM_022124: c.437C>T (p.(Pro146Leu)); c.3262G>A (p.(Val1088Met)); c.6911G>A (p.(Arg2304Gln)) | 765103490; 200632520; 201434373 | NA; EAS: 0.002; EAS: 0.0015 |
0.001; 0.003; 0.007 | 24.7; 24.3; 22.7 | LRT,MT,PP2,PR, SI; LRT,MA,mLR, mSVM,MT,PP2,SI; MT,SI |
| 7, 18 | MYO7A | NM_000260: c.4921G>A (p.(Glu1741Lys)) | 767975012 | EAS: 0.0002 | 0.003 | 26.2 | LRT,MT,PP2,PR |
| 8 | COL11A1 | NM_080629: c.4364A>C (p.(Lys1455Thr)) | 769350133 | EAS: 0.0004 | NA | 28.6 | FA,LRT,mLR, mSVM,MT,PP2, PR,SI |
| 8 | TECTA | NM_005422: c.2967C>A (p.(His989Gln) | 200821009 | EAS: 0.003 | 0.0014 | 20.4 | FA,LRT,mLR, mSVM,MT,PP2, PR,SI |
| 9 | IST1 | NM_001270976: c.737C>G (p.(Pro246Arg)) | 774343604 | EAS: 0.0002 | NA | 24.0 | LRT,MT,PP2,PR, SI |
| 13 | SLC12A2 | NM_001046: c.2977G>T (p.(Glu993*)) | NA | NA | NA | 60.0 | MT |
| 19 | MYO18B | NM_032608: c.2555C>T (p.(Ala852Val)) | NA | NA | NA | 26.1 | FA,LRT,mLR, mSVM,MA,MT, PP2,PR,SI |
| 23 | MYO18B | NM_032608: c.1982G>A (p.(Trp661*) | 372939044 | AFR: 0.0005 | NA | 44.0 | LRT/MT |
| 20 | CLDN9 | NM_020982: c.75C>G (p.(Cys25Trp)) | 368045321 | OTH: 0.0005 | 0.004 | 20.6 | FA,LRT,MA,mLR,mSVM,MT,PP2, PR,SI |
| 20, 24 | FLNA | NM_001110556: c.6350A>G (p.(Asn2117Ser)) | 375205247 | EAS: 0.002 | NA | 20.2 | FA,LRT,MT,PR |
| 22 | GREB1L | NM_001142966: c.3798C>G (p.(Ser1266Arg)) | 954005555 | EAS: 0.0006 | 0.003 | 16.6 | LRT,MA,MT,PR, SI |
| 22 | CBLN3 |
NM_001039771:
c.550C>T (p.(Arg184Cys)) |
562291434 | EAS: 0.0002 | NA | 32.0 | LRT,MT,PP2,PR, SI |
| 27 | GDPD5 | NM_030792: c.554G>A (p.(Arg185His)); c.404C>T (p.(Thr135Met)) | 745585758; 373413383 | ME: 0.003; AFR: 0.00002 | 0 (South Asia = 0.0007); NA | 23.1; 24.8 | LRT,MT,PP2; LRT,MA,MT,PP2 |
1. Bold font denotes candidate genes, while novel variants in known genes are in italics. 2. Variants identified in the Southeast Asian (SEA) population in the GenomeAsia 100k database were mostly from individuals of Filipino (n = 52) or Indonesian (n = 68) descent. MAF from Filipino alleles were identified in indigenous Negrito (Ati, Aeta) tribes, which are usually intermarried and are not representative of the general Filipino population. NA, not available/found; EAS, East Asian; AFR, African; ME, Middle Eastern; OTH, other; FA, FATHMM; LRT, likelihood ratio test; mLR, meta-logistic regression; mSVM, meta-support vector machine; MA, MutationAssessor; MT, MutationTaster; PP2, PolyPhen2; PR, PROVEAN; SI, SIFT.