chr10-62815939-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_000399.5(EGR2):c.91C>T(p.Leu31Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,172 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. L31V) has been classified as Uncertain significance.
Frequency
Consequence
NM_000399.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGR2 | NM_000399.5 | c.91C>T | p.Leu31Phe | missense_variant | 1/2 | ENST00000242480.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGR2 | ENST00000242480.4 | c.91C>T | p.Leu31Phe | missense_variant | 1/2 | 1 | NM_000399.5 | A1 | |
ENST00000493899.2 | n.572C>T | non_coding_transcript_exon_variant | 7/8 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152196Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251450Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135892
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461858Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727228
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74476
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 25, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Charcot-Marie-Tooth disease, type I Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 24, 2022 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 462789). This variant has not been reported in the literature in individuals affected with EGR2-related conditions. This variant is present in population databases (rs535186925, gnomAD 0.01%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 31 of the EGR2 protein (p.Leu31Phe). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at