TABLE 3.
Criteria considered for the pathogenicity classification of the novel identified variants.
| Gene | Mutation |
Classification | Frequency (gnomAD Ex) | Pathogenicity scoresa | Conservation score (GERP)b | Reputable source |
||
| Nucleotide change | Protein change | ClinVar | HGMDc | |||||
| ABCA4 (NM_000350.3) | c.2953G > A | p.(Gly985Arg) | Likely pathogenic | NF | 12 of 13 | 5.7199 | NA | NA |
| c.4880del | p.(Leu1627Argfs*35) | Pathogenic | 0.0000159 | NA | 5.6399 | Pathogenic | NA | |
| c.5714 + 1G > A | p.? | Pathogenic | 0.00000398 | NA | 4.7399 | Likely pathogenic | NA | |
| c.6310C > T | p.(Gln2104*) | Pathogenic | NF | NA | 6.0799 | NA | NA | |
| CEP290 (NM_025114.4) | c.7394_7395del | p.(Glu2465Valfs*2) | Pathogenic | 0.000598 | NA | 5.42 | NA | NA |
| CNGA3 (NM_001298.3) | c.673 + 5G > T | p.? | Likely pathogenic | 0.0000199 | NA | 5.09 | NA | NA |
| RPGRIP1 (NM_020366.3) | c.3339 + 5G > C | p.? | Likely pathogenic | NF | 2 of 2 | NA | Likely pathogenic | NA |
| CNGB1 (NM_001297.5) | c.2492 + 2T > G | p.? | Pathogenic | NF | NA | 5.4499 | NA | NA |
| CRB1 (NM_201253.3) | c.481G > A | p.(Ala161Thr) | Likely pathogenic | NF | 12 of 13 | 5.5199 | Uncertain significance | NA |
| PCARE (NM_001271 441.2) | c.656_665dup | p.(Ala223Argfs*38) | Likely pathogenic | 0.0000579 | NA | 1.8514 | NA | NA |
| EYS (NM_0011 42800.2) | c.1194del | p.(Gly399Aspfs*22) | Pathogenic | NF | NA | 6.07 | NA | NA |
| c.6882_6883del | p.(Gln2294Hisfs*3) | Pathogenic | NF | NA | 5.38 | NA | NA | |
| c.7736_7742del | p.(Thr2579Lysfs*36) | Pathogenic | 0.0000127 | NA | 4.01 | Likely pathogenic | NA | |
| c.8854del | p.(Thr2952Leufs*23) | Pathogenic | NF | NA | 4.57 | NA | NA | |
| GUCY2D (NM_000180.4) | c.1991A > G | p.(His664Arg) | Likely pathogenic | NF | 11 of 12 | 5.35 | NA | NA |
| GUCA1A (NM_000409.5) | c.66C > A | p.(Tyr22*) | Likely pathogenic | 0.00000795 | NA | 5.75 | Uncertain significance | NA |
| OTX2 (NM_001 270525.2) | c.638T > A | p.(Leu213*) | Pathogenic | NF | NA | 5.53 | NA | NA |
| PDE6A (NM_000440.3) | c.2144T > C | p.(Met715Thr) | Likely pathogenic | 0.000231 | 12 of 13 | 5.32 | Uncertain significance | NA |
| PDE6B (NM_000283.4) | c.1920 + 1G > A | p.? | Pathogenic | NF | NA | 4.19 | NA | NA |
| c.2470_2478del | p.(Lys824_Glu826del) | Uncertain significance | 0.000128 | NA | 4.1599 | NA | NA | |
| POC1B (NM_172240.3) | c.1079_1080del | p.(Pro360Argfs*8) | Pathogenic | 0.0000145 | NA | 5.69 | NA | NA |
| PROM1 (NM_006017.2) | exon 11 del | p.? | Pathogenic | NF | NA | NA | NA | NA |
| PRPH2 (NM_000322.5) | c.440dup | p.(Gly148Trpfs*29) | Pathogenic | NF | NA | 5.8699 | NA | NA |
| c.647C > A | p.(Pro216His) | Likely pathogenic | NF | 12 of 13 | 5.0999 | NA | NA | |
| RHO (NM_000539.3) | c.670G > A | p.(Gly224Arg) | Likely pathogenic | 0.0000159 | 12 of 13 | 5.0399 | NA | NA |
| RPGR (NM_001 034853.2) | c.1366del | p.(Gln456Lysfs*20) | Pathogenic | NF | NA | 4.73 | NA | NA |
| USH2A (NM_206933.4) | c.4955C > T | p.(Pro1652Leu) | Likely pathogenic | 0.000016 | 10 of 13 | 5.21 | NA | NA |
| c.6957 + 1G > C | p.? | Pathogenic | NF | NA | 5.8099 | NA | NA | |
| c.13894C > T | p.(Pro4632Ser) | Likely pathogenic | 0.00000797 | 8 of 13 | 5.21 | NA | NA | |
Column “Classification” refers to classification according to AMCG. aPathogenicity Scores from https://varsome.com/for missense variants (accessed November 2020) (BayesDel_addAF, DANN, DEOGEN2, EIGEN, FATHMM-MKL, LIST-S2, M-CAP, MVP, MutationAssessor, MutationTaster, PrimateAI, REVEL, and SIFT). Represent predictors supporting the pathogenic effect against the total of available predictors. bGERP conservation score based on the reduction in the number of substitutions in the multi-species sequence alignment compared to the neutral expectation using the genomes of 35 mammals. Range: -12.3 to 6.17 (most conserved). cHGMD public version (accessed November 2020). p.?, unknown protein effect; NF, no found; NA, not applicable. The “*” symbol corresponds to: stop-codon according to the format of mutations nomenclature from the Human Genome Variation Society (HGVS).