17-8003060-G-A
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_000180.4(GUCY2D):c.13G>A(p.Ala5Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,373,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000180.4 missense
Scores
Clinical Significance
Conservation
Publications
- cone-rod dystrophyInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
- GUCY2D-related dominant retinopathyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- GUCY2D-related recessive retinopathyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- Leber congenital amaurosis 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- cone-rod dystrophy 6Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- night blindness, congenital stationary, type1iInheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Leber congenital amaurosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- central areolar choroidal dystrophyInheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.0000233 AC: 32AN: 1373764Hom.: 0 Cov.: 32 AF XY: 0.0000251 AC XY: 17AN XY: 677826 show subpopulations
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Cone-rod dystrophy 6;C2931258:Leber congenital amaurosis 1 Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with GUCY2D-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces alanine with threonine at codon 5 of the GUCY2D protein (p.Ala5Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at