Table 2.
Disease-causing variants: evaluation and classification.
| Family ID | Gene | cDNA change | Protein change | Pathogenicity | Minor allele frequency (gnomAD) | ClinVar | HGMD accession no. | ACMG-based classification | ||
|---|---|---|---|---|---|---|---|---|---|---|
| MutationTaster | SIFT | PolyPhen-2 | ||||||||
| Retinal dystrophies (isolated and syndromic forms) | ||||||||||
| TR21 | ABCA4 | NM_000350.2:c.[5512C > G;5882G > A] | p.[(His1838Asp;Gly1961Glu)] | Deleterious (0.999);(0.999)a | Deleterious (0.02);(0.00)a | Deleterious (1.00);(1.00)a | 1/246168 (4.062e−6); 1292/277186 (0.004661)a | SCV000924646.1 | CM1311140; CM970016a | n.d. (complex allele) |
| AQ33/34 | CRB1 | NM_201253.3:c.2230C > T | p.(Arg744Ter) | Deleterious (1.000) | – | – | 3/245674 (1.221e−5) | SCV000924647.1 | BM1462770 | Pathogenic |
| AQ24 | CRB1 | NM_201253.3:c.2673C > A | p.(Cys891Ter) | Deleterious (1.000) | – | – | 1/120058 (ExAC) (0.000008329) | SCV000924648.1 | Novel | Pathogenic |
| AQ10 & AQ55 | CRB1 | NM_201253.3:c.3307G > A | p.(Gly1103Arg) | Deleterious (0.204) | Tolerated (0.12) | Deleterious (0.998) | 7/245136 (2.856e−5) | SCV000924649.1 | CM040718 | Pathogenic |
| AQ11/12 | CNGA3 | NM_001298.2:c.985G > T | p.(Gly329Cys) | Deleterious (0.999) | Deleterious (0.00) | Deleterious (1.000) | – | SCV000924650.1 | CM1110706 | Pathogenic |
| AQ23 | CNGA3 | NM_001298.2:c.940_942delATCb | p.(Ile314del) | Deleterious (0.999) | – | – | 6/246266 (2.436e−5) | SCV000924651.1 | CD014652 | Likely pathogenic |
| AQ08 | FAM161A | NM_001201543.2:c.1003C > T | p.(Arg335Ter) | Deleterious (1.000) | – | – | 4/277166 (1.443e−5) | SCV000924652.1 | CM142945 | Pathogenic |
| AQ09 | ADGRV1c | NM_032119.4:c.14315C > G | p.(Ser4772Ter) | Deleterious (1.000) | – | – | – | SCV000924653.1 | Novel | Pathogenic |
| AQ20 | RLBP1 | NM_000326.4:c.79delA | p.(Thr27Profs*26) | Deleterious (1.000) | – | – | – | SCV000924654.1 | Novel | Pathogenic |
| AQ53 | RPGRIP1 | NM_020366.3:c.1107delA | p.(Glu370Asnfs*5) | Deleterious (1.000) | – | – | – | SCV000924655.1 | CD012276 | Pathogenic |
| AQ06 | RDH5 | NM_002905.4:c.382G > A | p.(Asp128Asn) | Deleterious (0.999) | Tolerated (0.09) | Deleterious (1.000) | 2/243954 (8.198e−6) | SCV000924656.1 | CM077621 | Pathogenic |
| TR11 | SPATA7 | NM_018418.4:c.1–23706_373-709delinsTGG NC_000014.9:88,362,113_88,425,523delinsTGG | – | – | – | – | – | SCV000924657.1 | CG152189 | Pathogenic |
| Osteopetrosis (with complete vision loss) | ||||||||||
| AQ46 | SNX10 | NM_001199835.1:c.284G > A | p.(Arg95His) | Tolerated (0.968) | Tolerated (0.55) | Deleterious (1.000) | – | SCV000924658.1 | CM152582 | Likely pathogenic |
| Developmental malformations of the eye | ||||||||||
| AQ52 | VSX2 | NM_182894.2:c.679C > T | p.(Arg227Trp) | Deleterious (0.999) | Deleterious (0.01) | Deleterious (1.000) | 3/245904 (1.22e−5) | SCV000924659.1 | CM042327 | Pathogenic |
| MA08 | PXDN | NM_012293.3:c.2459A > G | p.(Gln820Arg) | Deleterious (0.999) | Deleterious (0.01) | Deleterious (0.992) | – | SCV000924660.1 | Novel | Likely pathogenic |
| Collagenopathies | ||||||||||
| AQ48 | COL9A2 | NM_001852.4:c.1774G > A | p.(Gly592Ser) | Deleterious (0.999) | Deleterious (0.00) | Deleterious (1.000) | 2/227220 (8.802e−6) | SCV000924661.1 | Novel | Likely pathogenic |
| COL18A1 | NM_130445.2:c.3514_3515delCT | p.(Leu1172Valfs*72) | Deleterious (1.000) | – | – | 66/222428 (0.0002967) | SCV000924662.1 | CD023246 | Pathogenic | |
| Congenital cataract | ||||||||||
| AQ21 | GALK1 | NM_000154.1:c.678delT | p.(Asn226Lysfs*38) | Deleterious (1.000) | – | – | – | SCV000924663.1 | Novel | Pathogenic |
| Foveal hypoplasia and infantile nystagmus (novel disease entity) | ||||||||||
| TR16 | AHR | NM_001621.5:c.1861C > T | p.(Gln621Ter) | Deleterious (1.000) | – | – | – | SCV000924664.1 | Novel | Pathogenic |
aPathogenicity score, minor allele frequency, and HGMD accession no. provided for each substitution in ABCA4 individually
bCorresponds to c. 934-936delATC in ref. [24]
cAlternative symbol: GPR98