chr10-62813217-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000399.5(EGR2):c.1421G>A(p.Arg474Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000383 in 1,566,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R474W) has been classified as Uncertain significance.
Frequency
Consequence
NM_000399.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGR2 | NM_000399.5 | c.1421G>A | p.Arg474Gln | missense_variant | 2/2 | ENST00000242480.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGR2 | ENST00000242480.4 | c.1421G>A | p.Arg474Gln | missense_variant | 2/2 | 1 | NM_000399.5 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000959 AC: 2AN: 208494Hom.: 0 AF XY: 0.0000180 AC XY: 2AN XY: 111278
GnomAD4 exome AF: 0.00000212 AC: 3AN: 1414106Hom.: 0 Cov.: 31 AF XY: 0.00000429 AC XY: 3AN XY: 700036
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74368
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease, type I Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 474 of the EGR2 protein (p.Arg474Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with EGR2-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on EGR2 protein function. 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