chr2-27364467-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001034116.2(EIF2B4):c.1505C>T(p.Thr502Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T502T) has been classified as Likely benign.
Frequency
Consequence
NM_001034116.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EIF2B4 | NM_001034116.2 | c.1505C>T | p.Thr502Met | missense_variant | 13/13 | ENST00000347454.9 | |
GTF3C2-AS2 | NR_183825.1 | n.1746-2957G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EIF2B4 | ENST00000347454.9 | c.1505C>T | p.Thr502Met | missense_variant | 13/13 | 1 | NM_001034116.2 | P4 | |
GTF3C2-AS2 | ENST00000412749.1 | n.201-2957G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251384Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135878
GnomAD4 exome AF: 0.0000458 AC: 67AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 28AN XY: 727246
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Vanishing white matter disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Oct 25, 2018 | The EIF2B4 c.1502C>T (p.Thr501Met) variant is a missense variant that has been reported in single study and is found in one individual with leukoencephalopathy with vanishing white matter in a compound heterozygous state with a missense variant (Zhang et al. 2015). The p.Thr501Met variant is inherited from the unaffected father. The p.Thr501Met variant is absent from 100 controls and is found at a frequency of 0.000027 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the limited evidence, the p.Thr501Met variant is classified as a variant of unknown significance but suspicious for pathogenicity for childhood ataxia with central nervous system hypomyelination/vanishing white matter. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at