TABLE 2.
51 benign or likely benign variants in RPGR from 101 unrelated families (based on NM_001034853).
| Variants | Exon | Nucleotide | Effect | ➀ | ➁ | ➂ | ➃ | gnomAD | No. of probands | Diagnosis | Novel or | Evidence | |||
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| change | AF | Hemi | EA | Hemi | (reported)∮ | Known | |||||||||
| Missense | |||||||||||||||
| 1 | ORF15 | c.1910G>A | p.S637N | B | N | 0.055 | 23.6 | NA | NA | NA | NA | 1(1) | HM | Known | 3 |
| 2 | ORF15 | c.1930G>A | p.V644M | B | N | 0.004 | 9.241 | NA | NA | NA | NA | 1 | RP | Novel | 1, 3, 5 |
| 3 | ORF15 | c.1957G>A | p.G653S | B | N | 0.019 | 10.57 | NA | NA | NA | NA | 1 | BCD | Novel | 2, 3, 5 |
| 4 | ORF15 | c.1967A>T | p.D656V | B | N | 0.043 | 16.41 | NA | NA | NA | NA | 1(1) | HM | Known | 3 |
| 5 | ORF15 | c.2135A>G | p.Q712R | B | N | 0.038 | 0.077 | 9/157035 | 2 | 9/12249 | 2 | 8(1) | N, HM, RB, ONH, G, HYP | Known | 2, 3, 4, 5, 6 |
| 6 | ORF15 | c.2200G>A | p.E734K | P | N | 0.04 | 18.53 | 6/117024 | 1 | 5/8773 | 1 | 5(1) | G, NYS, HM | Known | 2, 3, 4, 5 |
| 7 | ORF15 | c.2342C>T | p.A781V | B | N | 0.082 | 5.756 | 11/126393 | 4 | 0/9010 | 0 | 1 | RP | Novel | 3, 4 |
| 8 | ORF15 | c.2357A>C | p.K786T | B | N | 0.013 | 13.68 | NA | NA | NA | NA | 1 | Best | Novel | 2, 3, 5 |
| 9 | ORF15 | c.2606A>G | p.E869G | B | N | 0.062 | 14.86 | 25/40040 | 0 | 0/3847 | 0 | 1 | RP | Novel | 3, 4 |
| 10 | ORF15 | c.2995G>T | p.G999W | P | N | 0.025 | 17.62 | 1/71397 | 0 | 1/7897 | 0 | 1 | RP | Novel | 3, 4, 5 |
| 11 | ORF15 | c.3035A>G | p.E1012G | B | N | 0.031 | 12.1 | 5/110513 | 2 | 5/9144 | 2 | 2 | RB, RP | Novel | 2, 3, 4, 5 |
| 12 | ORF15 | c.3088G>A | p.G1030R | B | N | 0.046 | 15.2 | NA | NA | NA | NA | 1 | RP | Novel | 1, 3, 5 |
| 13 | ORF15 | c.3122A>G | p.E1041G | B | N | 0.04 | 14.35 | NA | NA | NA | NA | 2 | LCA, HM | Novel | 1, 3 |
| 14 | ORF15 | c.3220G>A | p.E1074K | B | N | 0.034 | 14.59 | 3/181654 | 1 | 2/13859 | 1 | 1 | G | Novel | 2, 3, 4 |
| 15 | ORF15 | c.3271A>T | p.I1091L | B | N | 0.006 | 10.61 | NA | NA | NA | NA | 2 | N, RB | Novel | 2, 3, 6 |
| 16 | ORF15 | c.3439C>G | p.H1147D | P | N | 0.257 | 24.1 | NA | NA | NA | NA | 1 | RP | Novel | 3 |
| In-frame | |||||||||||||||
| 1 | ORF15 | c.2360_2362del | p.G787del | / | / | / | / | 3/127259 | 0 | 3/9008 | 0 | 1 | HM | Novel | 4 |
| 2 | ORF15 | c.2447_2461del | p.G816_E820del | / | / | / | / | 123/103374 | 16 | 2/7866 | 1 | 4(1) | CORD, RP, RB, HM | Known | 2, 4 |
| 3 | ORF15 | c.2952_2954del | p.E985del | / | / | / | / | 2/52677 | 1 | 1/6728 | 0 | 1 | LCA | Novel | 4 |
| 4 | ORF15 | c.3032_3043del | p.G1011_E1014del | / | / | / | / | 3/116321 | 0 | 1/9309 | 0 | 1 | HM | Novel | 4 |
| 5 | ORF15 | c.3051_3053del | p.E1018del | / | / | / | / | 547/119184 | 118 | 1/9395 | 1 | 1 | NYS | Novel | 4 |
| 6 | ORF15 | c.3105_3122delins† | p.E1037_E1041delins# | / | / | / | / | NA | NA | NA | NA | 7 | N, HM, RD, FEVR, RP | Novel | 1, 2, 6 |
| 7 | ORF15 | c.3123_3125del | p.E1042del | / | / | / | / | 25/191580 | 6 | 2/14266 | 0 | 2(1) | RP | Known | 4 |
| 8 | ORF15 | c.3133_3135del | p.E1045del | / | / | / | / | 4/176793 | 3 | 0/13596 | 0 | 1 | RP | Novel | NA |
| 9 | ORF15 | c.3170_3172del | p.R1057del | / | / | / | / | 10/201586 | 5 | 1/14789 | 0 | 1 | RP | Novel | 4 |
| 10 | ORF15 | c.3180_3182del | p.E1066del | / | / | / | / | 2/181016 | 0 | 0/13852 | 0 | 1 | HM | Novel | NA |
| 11 | ORF15 | c.3189_3191del | p.E1066del | / | / | / | / | 2/181292 | 0 | 1/13854 | 0 | 1 | G | Novel | 2, 4 |
| 12 | ORF15 | c.3195_3197del | p.E1066del | / | / | / | / | 2/181292 | 0 | 1/13854 | 0 | 1 | HM | Novel | 4 |
| 13 | ORF15 | c.3225_3227del | p.E1076del | / | / | / | / | 1/181925 | 0 | 0/13860 | 0 | 1 | HM | Novel | NA |
| Exon1-14 | |||||||||||||||
| 1 | 1 | c.7G>A | p.E3K | P | N | 0.127 | 22.2 | NA | NA | NA | NA | 1 | G | Novel | 2, 3 |
| 2 | 2 | c.37G>A | p.A13T | D | D | 0.485 | 25.3 | NA | NA | NA | NA | 1 | FEVR | Novel | 2 |
| 3 | 2 | c.112G>A | p.V38I | B | N | 0.051 | 0.066 | NA | NA | NA | NA | 1 | LD | Novel | 2, 3, 5 |
| 4 | 4 | c.277G>T | p.A93S | D | D | 0.59 | 24.4 | 1/182876 | 1 | 1/13846 | 1 | 4 | RD, HM, COD, CD | Novel | 1, 2, 4, 5 |
| 5 | 6 | c.522A>T | p.L174F | D | D | 0.55 | 15.94 | NA | NA | NA | NA | 1 | N | Novel | 6 |
| 6 | 7 | c.738C>G | p.I246M | P | N | 0.404 | 17.84 | NA | NA | NA | NA | 1 | HM | Novel | 3 |
| 7 | 8 | c.782A>C | p.N261T | B | N | 0.19 | 7.487 | 4/180617 | 2 | 4/13651 | 2 | 4 | N, RP, RD, HM | Novel | 2, 3, 4, 5, 6 |
| 8 | 7 | c.727G>A | p.E243K | P | N | 0.33 | 23.1 | NA | NA | NA | NA | 1 | G | Novel | 2 |
| 9 | 10 | c.1163C>T | p.A388V | B | N | 0.049 | 5.981 | 44/183213 | 14 | 0/13847 | 0 | 2 | G, HM | Novel | 2, 3, 4 |
| 10 | 11 | c.1270A>G | p.M424V | B | D | 0.12 | 6.942 | 3/182944 | 0 | 0/13818 | 0 | 1 | PHPV | Novel | 2, 3 |
| 11 | 11 | c.1282C>G | p.L428V | P | N | 0.129 | 14.6 | 35/204797 | 14 | 35/14807 | 14 | 8(1) | G, HM, OA, RP, RD, RRD | Known | 2, 3, 4, 5 |
| 12 | 11 | c.1331A>G | p.N444S | B | N | 0.012 | 0.002 | 2/183351 | 0 | 0/13858 | 0 | 1 | RRD | Novel | 2, 3, 5 |
| 13 | 11 | c.1367A>G | p.Q456R | B | N | 0.016 | 0.052 | 1704/205075 | 594 | 0/14852 | 0 | 1 | G | known | 2, 3, 4 |
| 14 | 13 | c.1519A>G | p.S507G | P | D | 0.046 | 22 | 4/164448 | 0 | 4/12070 | 0 | 2 | LCA, G | Novel | 1, 2, 4 |
| 15 | 13 | c.1561C>G | p.Q521E | B | N | 0.046 | 16.13 | 5/171108 | 3 | 5/12659 | 3 | 6 | G, MC, RB, HYP, HM | Novel | 1, 2, 3, 4 |
| 16 | 14 | c.1585A>G | p.I529V | B | N | 0.006 | 0.002 | 2/181278 | 0 | 1/13849 | 0 | 3 | NYS, HM, LCA | Novel | 2, 3 |
| 17 | 14 | c.1622A>G | p.N541S | B | N | 0.016 | 0.343 | NA | NA | NA | NA | 1 | RRD | Novel | 2, 3, 5 |
| 18 | 14 | c.1628A>G | p.D543G | B | N | 0.011 | 4.167 | NA | NA | NA | NA | 1 | RP | Novel | 3 |
| 19 | 14 | c.1630A>G | p.S544G | P | N | 0.049 | 19.15 | 2/182957 | 1 | 1/13858 | 0 | 3(1) | N, G, HM | Known | 2, 3, 4, 6 |
| 20 | 14 | c.1720A>G | p.T574A | B | N | 0.013 | 0.527 | NA | NA | NA | NA | 1 | LCA | Novel | 3, 5 |
| 21 | 14 | c.1721C>T | p.T574M | B | N | 0.008 | 1.128 | 23/204508 | 9 | 1/14838 | 0 | 1 | HM | Novel | 3, 4 |
| 22 | 10 | c.1117_1119dupAAA | p.K373dup | / | / | / | / | 12/182610 | 6 | 12/13812 | 6 | 3 | MD, HM, RB | Novel | 1, 2, 4 |
AF, allele frequency; CD, corneal degeneration; COD, cone dystrophy; CORD, cone-rod dystrophy; EA, East Asians; G, glaucoma; HM, high myopia; Hyp, Hypermetropia; LCA, Leber congenital amaurosis; LD, lens dislocation; MC, macular coloboma; MD, macular degeneration; N, normal; NA, not available; NYS, nystagmus; OA, ocular albinism; ONH, Optic nerve hypoplasia; PHPV, Persistent Hyperplastic Primary Vitreous; RB, retinoblastoma; RD, retinal diseases; RP, retinitis pigmentosa; RRD, Rhegmatogenous Retinal Detachment; /, not applicable; FEVR, familial exudative vitreoretinopathy; †AGAAAGGGAAAAGGAGGG; #ArgGluLysGluGly; ()∮ Previously reported by our lab. 1, polyphen-2 HVAR; 2, PROVEAN; 3, REVEL; 4, CADD. gnomAD, genome aggregation database; HGMD, the Human Gene Mutation Database.
Evidence that variant is benign or likely benign: 1 = does not segregate with inherited eye diseases in one or more families (males with variants were unaffected); 2 = variant identified in one or more families with eye disease other than RP, CORD, COD, MD, or HM; 3 = at least two of four predicting tools are benign; 4 = MAF ≥ 4.7 × 10–5 in gnomAD database; 5 = identified other known IRD pathogenic variants; 6 = verified in controls.
All variants are not recorded in HGMD except the variant c.1630A>G.