chr2-27364467-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001034116.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Ensembl
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
not provided Pathogenic:1
Reported using alternate nomenclature (c.1565C>T, p.T522M) with a variant on the opposite allele (in trans) in a patient with vanishing white matter disease in published literature (PMID: 25761052); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34745209, 25761052) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at