rs28937596
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_003907.3(EIF2B5):āc.1882T>Cā(p.Trp628Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
EIF2B5
NM_003907.3 missense
NM_003907.3 missense
Scores
9
8
2
Clinical Significance
Conservation
PhyloP100: 7.28
Genes affected
EIF2B5 (HGNC:3261): (eukaryotic translation initiation factor 2B subunit epsilon) This gene encodes one of five subunits of eukaryotic translation initiation factor 2B (EIF2B), a GTP exchange factor for eukaryotic initiation factor 2 and an essential regulator for protein synthesis. Mutations in this gene and the genes encoding other EIF2B subunits have been associated with leukoencephalopathy with vanishing white matter. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.97
PP5
Variant 3-184144111-T-C is Pathogenic according to our data. Variant chr3-184144111-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 5943.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EIF2B5 | NM_003907.3 | c.1882T>C | p.Trp628Arg | missense_variant | 14/16 | ENST00000648915.2 | NP_003898.2 | |
EIF2B5 | XM_011513265.1 | c.1132T>C | p.Trp378Arg | missense_variant | 10/12 | XP_011511567.1 | ||
EIF2B5 | XM_011513266.4 | c.1045T>C | p.Trp349Arg | missense_variant | 9/11 | XP_011511568.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EIF2B5 | ENST00000648915.2 | c.1882T>C | p.Trp628Arg | missense_variant | 14/16 | NM_003907.3 | ENSP00000497160.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 exome
AF:
AC:
1
AN:
1461886
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
727248
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Leukoencephalopathy with vanishing white matter 5 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2001 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.
REVEL
Pathogenic
Sift
Uncertain
D;.;.
Sift4G
Pathogenic
D;.;.
Polyphen
D;.;D
Vest4
MutPred
Gain of methylation at W628 (P = 0.0382);.;Gain of methylation at W628 (P = 0.0382);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at