Table 1.
Summary of genetic analyses for 26 EYS variants.
| No. | Variant | Variant type | Family count (%*) | AC* | AF* | Mean read depth | Coverage (≥15 reads) | AF in general databases | ACMG classification | Reference | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HGVD | iJGVD 3.5k | gnomAD EA | gnomAD Total | ||||||||||
| 1 | c.2528 G > A, p.(Gly843Glu) | Missense | 26 (42.6%) | 32 | 26.23% | 37.24 | 99.87% | 2.25% | 1.7000% | 0.0391% | 0.0026% | LP | 25 |
| 2 | c.4957dupA, p.(Ser1653Lysfs*2) | Frameshift | 22 (36.1%) | 29 | 23.77% | 38.27 | 100.00% | 0.2084% | 0.0000% | 0.0098% | 0.0007% | P | 15,20,25,32 |
| 3 | c.8805 C > A, p.(Tyr2935*) | Nonsense | 14 (23.0%) | 17 | 13.93% | 37.11 | 100.00% | 0.2901% | 0.1700% | 0.0293% | 0.0020% | P | 15,20,25 |
| 4 | c.7394 C > G, p.(Thr2465Ser) | Missense | 12 (19.7%) | 15 | 12.30% | 36.70 | 99.74% | 3.0468% | 2.9000% | 0.1465% | 0.0126% | US | Novel†20 |
| 5 | c.6557 G > A, p.(Gly2186Glu) | Missense | 7 (11.5%) | 7 | 5.74% | 35.09 | 99.15% | 0.0000% | 0.0000% | 0.0497% | 0.0035% | LP | 14,20,32 |
| 6 | c.6563 T > C, p.(Ile2188Thr) | Missense | 5 (8.2%) | 6 | 4.92% | 32.15 | 97.12% | 0.0000% | 0.1000% | NA | NA | US | 15 |
| 7 | c.1211dupA, p.(Asn404Lysfs*3) | Frameshift | 3 (4.9%) | 3 | 2.46% | 48.45 | 99.80% | 0.0000% | 0.0000% | 0.0000% | 0.0016% | P | 25,33 |
| 8 | c.632 G > A, p.(Cys211Tyr) | Missense | 2 (3.3%) | 2 | 1.64% | 35.97 | 99.41% | 0.0000% | 0.0300% | NA | NA | LP | 15 |
| 9 | c.7665_7666del, p.(Tyr2555*) | Nonsense | 2 (3.3%) | 2 | 1.64% | 33.26 | 93.72% | 0.0000% | 0.0000% | NA | NA | P | 25 |
| 10 | c.5644 + 5 G > A | Splicing | 1 (1.6%) | 1 | 0.82% | 31.63 | 93.85% | 0.0000% | 0.0000% | NA | NA | P | 34 |
| 11 | c.3809 T > G, p.(Val1270Gly) | Missense | 1 (1.6%) | 1 | 0.82% | 35.88 | 99.93% | 0.4570% | 0.0455% | 0.0492% | 0.0033% | US | 25 |
| 12 | c.5027 C > G, p.(Ser1676*) | Nonsense | 1 (1.6%) | 1 | 0.82% | 35.37 | 98.50% | 0.0000% | 0.0000% | 0.0000% | 0.0000% | P | This study |
| 13 | c.7002 C > A, p.(Cys2334*) | Nonsense | 1 (1.6%) | 1 | 0.82% | 27.08 | 90.26% | 0.0000% | 0.0100% | NA | NA | P | 35 |
| 14 | c.6714del, p.(Ile2239Serfs*17) | Frameshift | 1 (1.6%) | 1 | 0.82% | 27.97 | 91.69% | 0.0000% | 0.0000% | 0.0098% | 0.0039% | P | 5,17,27,35 |
| 15 | c.1485_1493delinsCGAAAAG, p.(Val495Glufs*13) | Frameshift | 1 (1.6%) | 1 | 0.82% | 33.67 | 99.22% | 0.0000% | 0.0000% | NA | NA | P | 25 |
| 16 | c.137 C > T, p.(Thr46Ile) | Missense | 1 (1.6%) | 1 | 0.82% | 38.23 | 99.28% | 0.0000% | 0.0000% | NA | NA | US | This study |
| 17 | c.9186_9187del, p.(Asn3062Lysfs*9) | Frameshift | 1 (1.6%) | 1 | 0.82% | 39.32 | 99.61% | 0.0000% | 0.0000% | 0.0000% | 0.0013% | P | 36 |
| 18 | c.8608 A > T, p.(Asn2870Tyr) | Missense | 1 (1.6%) | 1 | 0.82% | 48.93 | 100.00% | 0.0000% | 0.0000% | NA | NA | US | This study |
| 19 | c.141 A > T, p.(Glu47Asp) | Missense | 1 (1.6%) | 1 | 0.82% | 38.97 | 100.00% | 0.0000% | 0.0100% | NA | NA | US | 15,35 |
| 20 | c.4022del, p.(Ser1341Phefs*11) | Frameshift | 1 (1.6%) | 1 | 0.82% | 43.99 | 100.00% | 0.0000% | 0.0000% | NA | NA | P | 35 |
| 21 | c.8278 C > T, p.(Arg2760Cys) | Missense | 1 (1.6%) | 1 | 0.82% | 39.08 | 99.80% | 0.0000% | 0.0000% | 0.0000% | 0.0000% | US | This study |
| 22 | c.8516dupA, p.(Asn2839Lysfs*2) | Frameshift | 1 (1.6%) | 1 | 0.82% | 24.03 | 87.22% | 0.0000% | 0.0000% | NA | NA | P | This study |
| 23 | c.7609 G > A, p.(Ala2537Thr) | Missense | 1 (1.6%) | 1 | 0.82% | 33.56 | 98.63% | 0.5013% | 0.2300% | 0.2678% | 0.0266% | US | 36,37 |
| 24 | c.2000G > A, p.(Arg667His) | Missense | 1 (1.6%) | 1 | 0.82% | 35.18 | 99.87% | 0.0000% | 0.0327% | 0.0000% | 0.0295% | US | 38 |
| 25 | c.7919 G > A, p.(Trp2640*) | Nonsense | 1 (1.6%) | 1 | 0.82% | 41.19 | 100.00% | 0.0000% | 0.0600% | 0.0000% | 0.0027% | P | 4,17,39 |
| 26 | c.7392dupT, p.(Thr2465Tyrfs*12) | Frameshift | 1 (1.6%) | 1 | 0.82% | 41.27 | 100.00% | 0.0000% | 0.0000% | NA | NA | P | This study |
AC = allele count; AF = allele frequency; EA = East Asian; ACMG = American College of Medical Genetics and Genomics; P = pathogenic; LP = likely pathogenic; US = uncertain significance; HGVD = Human Genetic Variation Database (http://www.genome.med.kyoto-u.ac.jp/SnpDB/; accessed on July 1, 2017); iJGVD 3.5k=Integrative Japanese Genome Variation 3.5k (https://ijgvd.megabank.tohoku.ac.jp/download_3.5kjpn/; accessed on July 1, 2017); gnomAD=the Genome Aggregation Database (http://gnomad.broadinstitute.org/; accessed on 1st of August, 2018).
*Number is this cohort; †: a variant listed in the cited reference, but not associated with the disease.