17-8003090-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.43G>A(p.Gly15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,524,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G15G) has been classified as Likely benign.
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 AF: 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 33 show subpopulations
GnomAD4 exome AF: 0.0000248 AC: 34AN: 1372496Hom.: 0 Cov.: 32 AF XY: 0.0000177 AC XY: 12AN XY: 677086 show subpopulations
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74314 show subpopulations
ClinVar
Submissions by phenotype
Cone-rod dystrophy 6;C2931258:Leber congenital amaurosis 1 Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 15 of the GUCY2D protein (p.Gly15Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GUCY2D-related conditions. Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt GUCY2D protein function with a negative predictive value of 95%. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at