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Table 2 LCA genes variants identified in Polish Patients

From: Novel gene variants in Polish patients with Leber congenital amaurosis (LCA)

Family no Mode of inheritance Gene Causative variations and coexisting variations Pathogenicity prediction in protein level Allele frequency (gnomAD browser) Reported in literature/ variants databases: LOVD, HGMD, ClinVar Molecular method of searching the variants
Nucleotide Exon/intron no Protein Status SIFT PROVEAN PolyPhen-2
1, 11 and 16 AR CEP290 c.2991+1655A>G i.26 p.Cys998* Het - - - None Yes/yes SNP-array1
    c.4882C>T e.37 p.Gln1628* Het - - - 12/172,352 Yes/yes  
2 AR CEP290 c.2991+1655A>G i.26 p.Cys998* Het - - - None Yes/yes NGS
    c.4962_4963del e.37 p.(Glu1656Asnfs*3) Het - - - 7/172,100 Yes/yes  
   LRAT c.236T<G e.2 p.(Leu79Trp) Het Tolerated (0.09) Neutral (− 1.249) Probably damaging (0.998) 1/251,328 No/no  
3 AR CEP290 c.3811C>T e.31 p.Arg1271* Het - - - 2/249,060 Yes/LOVD, HGMD SNP-array1
    c.4723A>T e.36 p.Lys1575* Het - - - 15/247,902 Yes/yes  
4 AR CEP290 c.2991+1655A>G i.26 p.Cys998* Het - - - None Yes/yes NGS
    c.6606_6618del e.48 p.(Ile2202Metfs*20) Het - - - None No/no  
5 AR CEP290 c.2991+1655A>G i.26 p.Cys998* Het - - - None Yes/yes SNP-array1
    c.4723A>T e.36 p.Lys1575* Het - - - 15/247,902 Yes/yes  
21 AR CEP290 c.2991+1655A>G i.26 p.Cys998* Het - - - None Yes/yes NGS
    c.5515_5518del e.40 p.(Glu1839Lysfs*11) Het - - - 3/258,898 No/LOVD, ClinVar  
8 AR GUCY2D c.1318_1319del e.4 p.(Gly440Ilefs*6) Het - - - None No/no NGS
    c.2302C>T e.12 p.(Arg768Trp) Het Damaging (0.00) Deleterious (− 7.478) Probably damaging (1.0) 40/282,714 Yes/yes  
   RPGRIP1 c.1414C>T   p.(Gln472*) Het - - - None No/no  
12 AR GUCY2D c.2943del e.15 p.Gly982Valfs Het - - - None No/ ClinVar SNP-array1
    c.3118C>T e.17 p.Arg1040Gly Het Damaging (0.00) Deleterious (− 6,486) Probably damaging (1.0) 2/237,808 Yes/HGMDClinVar  
15 AR GUCY2D c.2302C>T e.12 p.(Arg768Trp) Het Damaging (0.00) Deleterious (− 7.478) Probably damaging (1.0) 40/282,714 Yes/yes SNP-array1, NGS
    c.721+2T>Ca i.2 p.? Het - - - None No/no  
18 AR GUCY2D c.2943del e.15 p.Gly982Valfs Hom Damaging (0.00) Deleterious (− 7.665) Probably damaging (1.0) None No/ClinVar SNP-array1
6 AR RPE65 c.1451G>T e.14 p.(Gly484Val) Hom Damaging (0.00) Deleterious (− 8.348) Probably damaging (1.0) 3/248,526 No/no NGS
10 AR RPE65 c.304G>T e.4 p.Glu102* Hom - - - 9/251,366 Yes/yes NGS
13 AR RPE65 c.106del e.3 p.(Leu36Serfs*58) Het - - - 1/251,466 No/no NGS
    c.726-2A>Tb i.7 p.? Het - - - None No/no  
9 AR NMNAT1 c.59T>A e.2 p.Ile20Asn Het Damaging (0.00) Deleterious (− 5.269) Probably damaging (0.999) 1/251,144 Yes/yes SNP-array1, NGS
    c.769G>A e.5 p.Glu257Lys Het Tolerated (0.72) Neutral (− 2,313) Benign (0.089) 196/282,064 Yes/yes  
19 AR NMNAT1 c.65A>G e.2 p.(Asn22Ser) Het Tolerated (0.45) Deleterious (− 4.003) Probably damaging (0.989) None No/no NGS
    c.769G>A e.5 p.Glu257Lys Het Tolerated (0.72) Neutral (− 2.313) Benign (0.089) 196/282,064 Yes/yes  
   CEP290 c.226G<A e.4 p.(Ala76Thr) Het Damaging (0.00) Neutral (− 0.560) Probably damaging (1.0) 180/269,442 No/LOVD  
14 AR CRB1 c.2843G>A e.9 p.Cys948Tyr Hom Damaging (0.00) Deleterious (− 9.655) Probably damaging (0.998) 57/281,210 Yes/yes NGS
17 AR CRB1 c.2843G>A e.9 p.Cys948Tyr Hom Damaging (0.00) Deleterious (− 9.655) Probably damaging (0.998) 57/281,210 Yes/yes SNP-array1
7 AR RPGRIP1 c.1216del e.10 p.(Leu406Tyrfs*36) Hom - - - None No/no SNP-array1, NGS
22 AR RPGRIP1 c.1148_1151del e.9 p.(Glu383Alafs*19) Het - - - None No/no SNP-array1, NGS2
    c.2465_2468dup e.16 p.(Ala824Ilefs*11) Het - - - 1/249,180 No/no  
20 AD CRX c.571delT e.4 p.Tyr191fs*2 Het - - - None Yes/ClinVar SNP-array1
  1. Novel variants are marked in italic
  2. Hyphen “-”means that prediction in protein level was not performed for the variants (not necessary or improper for these variants). Allele frequency is listed according to gnomeAD Browser (Genome Aggregation Database)
  3. 1LCA mutation chip (SNP-microarray) based on the APEX approach (Asper Ophthalmics, Asper Biotech Ltd., Tartu, Estonia)
  4. 2 “Inherited Retinal Disorders NextGen Sequencing Panel” (31 genes) performed at the University of Pennsylvania at 2017
  5. a,bSplicing variants submitted to additional potential pathogenicity prediction in protein level analyses with the use of CADD and Fathmm software. The results of the analyses revealed that both variants are deleterious. For the variant c.721+2T>C in the GUCY2D gene the CADD score is 33, and the Fathmm score is 0.97. For the variant c.726-2A>T in the RPE65 gene the CADD score is 34 and the Fathmm score is 0.99