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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
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Orphanet Journal of Rare Diseases

ISSN: 1750-1172