GUCY2D A52S - GET-Evidence



(GUCY2D Ala52Ser)

Short summary

One publication suggested that this variant possibly causes Leber’s congenital amaurosis in a recessive manner, but the frequency data (36% in 1000 genomes) contradicts any significant pathogenic effect.

Variant evidence
Computational 1

This gene is associated with LCA.

See Perrault I et al. 1996 (8944027).

Functional -

The OR is 12.5 assuming that the controls were heterozygous. If the 1000 genomes is in Hardy Weinberg equilibrium, however, the OR is 0.825.

See Perrault I et al. 1996 (8944027), unpublished research (below).


This variant segregated with a consanguineous Tunisian family but no LOD available.

See Perrault I et al. 1996 (8944027).

Clinical importance
Severity -
Treatability -
Penetrance -


Low clinical importance, Uncertain benign

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern


Summary of published research, and additional commentary

The high frequency with which this variant occurs in the 1000 genomes data make it unlikely to be causative for leber congenital amaurosis. If the variant is in Hardy-Weinberg equilibrium, 15 of the 114 1000 genomes individuals would be homozygous. The OR would then be 0.825.

Allele frequency

  • T @ chr17:7906519: 21.0% (1659/7894) in EVS
  • Frequency shown in summary reports: 21.0% (1659/7894)


Perrault I, Rozet JM, Calvas P, Gerber S, Camuzat A, Dollfus H, Châtelin S, Souied E, Ghazi I, Leowski C, Bonnemaison M, Le Paslier D, Frézal J, Dufier JL, Pittler S, Munnich A, Kaplan J. Retinal-specific guanylate cyclase gene mutations in Leber's congenital amaurosis. Nat Genet. 1996 Dec;14(4):461-4. PubMed PMID: 8944027.

This variant segregated with autosomal recessive Leber congenital amaurosis type 1 in one of eight families analyzed, but it was also found (as a heterozygote?) in 2/100 controls. Because it was seen in controls, the authors note that it may simply be a rare polymorphism rather than disease-causing. LOD is not reported and cannot be calculated as the pedigree isn’t reported.



















Other external references

  • rs61749665
  • GeneTests records for the GUCY2D gene
    Leber Congenital Amaurosis
    Cone-Rod Dystrophy, Type 6
    GUCY2D-Related Leber Congenital Amaurosis
  • Score: 0.026 (benign)
    Web search results (15 hits -- see all)
  • Molecular Vision: Seong, Mol Vis 2008; 14:1429-1436. Table 2
    GUCY2D. c.154G>T (A52S) 0.75 [23] RPGRIP1. c.287C>A (P96Q) 0.05 [26] ... All polymorphic sequence variations in nine genes are presented here. Allele frequency ...
  • Leber's Congenital Amaurosis (LCA) genetic testing
    Ophthalmogenetic testing for retinal disorders - Usher Syndrome, Leber Congenital amaurosis, Retinitis Pigmentosa, Bardet Biedl Syndrome, ABCR gene
  • Genotyping Microarray (Disease Chip) for Leber Congenital ...
    (K192E and E1033Q in RPGRIP1, A52S and L782H in. GUCY2D , D90H in AIPL1), to facilitate ... analysis, such as the GUCY2D P701S variant described earlier, would ...
  • Genotyping Microarray (Disease Chip) for Leber Congenital ...
    Since the identification of guanylate cyclase 2D (GUCY2D)2 in 1996 as the first LCA gene, mutations in five ... E1033Q in RPGRIP1, A52S and L782H in GUCY2D, D90H in AIPL1), to ...
  • Leber congenital amaurosis genetic testing
    Nucleotide change G154T in gene GUCY2D exon 2 analyzed. by APEX. The signals corresponding ... causes amino acid change A52S. OPHTHALMICS. ...
  • Mendelian Inheritance in Man Document Reader
    ... a rat eye cDNA library and may be a homolog of the gene here designated GUCY2D. ... an alanine into a serine (A52S). Heterozygosity for the same mutation ...
  • EPOS - European Paediatric Ophthalmological Society
    11 Mutational analysis in Leber congenital amaurosis. Sitorus, R.1, Rosenberg, T.2, ... were found in the homozygous state in one index patient (A52S) from a ...
  • Type II- 95%
    ... CMTX1, moderate 11437164 HSD11B2 P80365 R186C 184 VAR_015637 PKC (0.550) AME 7593417 9661590 PKLR P30613 ... (0.500) uterine cancer GUCY2D Q02846 A52S 51 VAR_003435 MAPK (0.523) ...

Other in silico analyses

  • NBLOSUM100 score = –1
  • GET-Evidence autoscore = 4

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Gene search

"GENE" or "GENE A123C":

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