TABLE 1.
Genetic variants detected in the affected patient after the NGS analysis. Six of them were identified as synonymous variants or classified as benign/likely benign by in silico software. The variants in bold were selected because its genetic consequence according to the ACMG guidelines (Richards et al., 2015) and being predicted as pathogenic by several in silico software applications (ClinVar, PolyPhen, and SIFT). GRCh37 (hg 19) was considered as the reference. The RNA splicing effect in missense and synonymous variants was discarded by Alamut software.
| Gene | Chr | Coordinate | Freq | Read depth | Depth variant | HGVSc | HGVSp | Consequence | ClinVar | PolyPhen | SIFT | dbSNP ID | ACMG criteria | Classification |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ADGRV1 | 5 | 89,990,447 | 48,2 | 110 | 53 | NM_032119.3: c.7874G>A | p.Arg2625His | Missense | Likely benign | Benign (0.018) | rs201214794 | BA1, BS1, and BS2 | Class 1—benign | |
| ADGRV1 | 5 | 90,020,923 | 46,3 | 164 | 76 | NM_032119.3: c.9927T>G | p.Pro3309Pro | Synonymous | rs16869042 | BA1 and BS2 | Class 1—benign | |||
| CDH23 | 10 | 73,569,731 | 31 | 84 | 26 | NM_022124.5: c.8877C>T | p.Ile2959Ile | Synonymous | rs373709237 | PM2, BP7, and BP6 | Class 2—likely benign | |||
| GJA1 | 6 | 121,768,897 | 30,9 | 139 | 43 | NM_000165.3: c.904A>G | p.Asn302Asp | Missense | Benign (0.012) | Tolerated (0.16) | rs775532447 | PM2 and PP2 | Class 3—VUS | |
| GJA1 | 6 | 121,768,924 | 30,9 | 139 | 43 | NM_000165.3: c.932delC | p.Ala311ValfsTer37 | Frameshift | rs778110855 | PVS1 | Class 4—likely pathogenic | |||
| GJA1 | 6 | 121,769,050 | 30,5 | 141 | 43 | NM_000165.3: c.1057T>C | p.Leu353Leu | Synonymous | PM2, BP4, and BP7 | Class 2—likely benign | ||||
| MY O 7A | 11 | 76,883,797 | 25 | 12 | 3 | NM_000260.3: c.1801G>A | p.Ala601Thr | Missense | Benign (0.245) | Tolerated (0.34) | rs782481491 | PM2 | Class 3—VUS | |
| WFS1 | 4 | 6,303,573 | 49,1 | 322 | 158 | NM_006005.3: c.2051C>T | p.Ala684Val | Missense | Pathogenic | Probably damaging (0.992) | Deleterious (0) | rs387906930 | PM2, PM5, PM1, PP3, and PP5 | Class 5—pathogenic |
Chr and Coordinate, are the chromosome and coordinates where the gene is located. Freq indicates the variant frequency detected in sequencing. HGVSc and HGVSp shows the naming at DNA and protein levels according to HGVS convenctions.