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NM_001034116.2(EIF2B4):c.1070G>A (p.Arg357Gln) AND Vanishing white matter disease

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 28, 2018
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000004333.7

Allele description [Variation Report for NM_001034116.2(EIF2B4):c.1070G>A (p.Arg357Gln)]

NM_001034116.2(EIF2B4):c.1070G>A (p.Arg357Gln)

Genes:
GTF3C2-AS2:GTF3C2 antisense RNA 2 [Gene - HGNC]
EIF2B4:eukaryotic translation initiation factor 2B subunit delta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p23.3
Genomic location:
Preferred name:
NM_001034116.2(EIF2B4):c.1070G>A (p.Arg357Gln)
HGVS:
  • NC_000002.12:g.27366880C>T
  • NG_009305.1:g.8578G>A
  • NM_001034116.2:c.1070G>AMANE SELECT
  • NM_001318965.2:c.1133G>A
  • NM_001318966.2:c.1025G>A
  • NM_001318967.2:c.977G>A
  • NM_001318968.2:c.485G>A
  • NM_001318969.2:c.452G>A
  • NM_015636.4:c.1067G>A
  • NM_172195.4:c.1130G>A
  • NP_001029288.1:p.Arg357Gln
  • NP_001305894.1:p.Arg378Gln
  • NP_001305895.1:p.Arg342Gln
  • NP_001305896.1:p.Arg326Gln
  • NP_001305897.1:p.Arg162Gln
  • NP_001305898.1:p.Arg151Gln
  • NP_056451.3:p.Arg356Gln
  • NP_056451.3:p.Arg356Gln
  • NP_751945.2:p.Arg377Gln
  • NC_000002.11:g.27589747C>T
  • NM_015636.3:c.1067G>A
  • Q9UI10:p.Arg357Gln
Protein change:
R151Q; ARG357GLN
Links:
UniProtKB: Q9UI10#VAR_015407; OMIM: 606687.0001; dbSNP: rs113994033
NCBI 1000 Genomes Browser:
rs113994033
Molecular consequence:
  • NM_001034116.2:c.1070G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318965.2:c.1133G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318966.2:c.1025G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318967.2:c.977G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318968.2:c.485G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318969.2:c.452G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015636.4:c.1067G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172195.4:c.1130G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Vanishing white matter disease
Synonyms:
CACH syndrome; Childhood ataxia with diffuse central nervous system hypomyelination; Leukoencephalopathy with vanishing white matter; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0800448; MedGen: C1858991; Orphanet: 99853; OMIM: PS603896

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000914923Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)		Uncertain significance
(Nov 28, 2018) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in the genes encoding eukaryotic translation initiation factor 2B in Japanese patients with vanishing white matter disease.

Shimada S, Shimojima K, Sangu N, Hoshino A, Hachiya Y, Ohto T, Hashi Y, Nishida K, Mitani M, Kinjo S, Tsurusaki Y, Matsumoto N, Morimoto M, Yamamoto T.

Brain Dev. 2015 Nov;37(10):960-6. doi: 10.1016/j.braindev.2015.03.003. Epub 2015 Apr 3.

PubMed [citation]
PMID:
25843247

Mutations in each of the five subunits of translation initiation factor eIF2B can cause leukoencephalopathy with vanishing white matter.

van der Knaap MS, Leegwater PA, Könst AA, Visser A, Naidu S, Oudejans CB, Schutgens RB, Pronk JC.

Ann Neurol. 2002 Feb;51(2):264-70.

PubMed [citation]
PMID:
11835386

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000914923.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The EIF2B4 c.1067G>A (p.Arg356Gln) missense variant has been reported in three individuals, including a sibling pair, affected with white matter vanishing disease, all in a compound heterozygous state with a missense variant. The variant was present in one unaffected parent in a heterozygous state, absent from 120 control chromosomes and is reported at a frequency of 0.000012 in the Total population of the Genome Aggregation Database. Based on the limited evidence, the p.Arg356Gln 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 14, 2024