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NM_001034116.2(EIF2B4):c.1393T>C (p.Cys465Arg) AND Leukoencephalopathy with vanishing white matter 4

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 1, 2003
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV003221397.10

Allele description [Variation Report for NM_001034116.2(EIF2B4):c.1393T>C (p.Cys465Arg)]

NM_001034116.2(EIF2B4):c.1393T>C (p.Cys465Arg)

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.1393T>C (p.Cys465Arg)
HGVS:
  • NC_000002.12:g.27364579A>G
  • NG_009305.1:g.10879T>C
  • NM_001034116.2:c.1393T>CMANE SELECT
  • NM_001318965.2:c.1456T>C
  • NM_001318966.2:c.1348T>C
  • NM_001318967.2:c.1300T>C
  • NM_001318968.2:c.808T>C
  • NM_001318969.2:c.775T>C
  • NM_015636.4:c.1390T>C
  • NM_172195.4:c.1453T>C
  • NP_001029288.1:p.Cys465Arg
  • NP_001305894.1:p.Cys486Arg
  • NP_001305895.1:p.Cys450Arg
  • NP_001305896.1:p.Cys434Arg
  • NP_001305897.1:p.Cys270Arg
  • NP_001305898.1:p.Cys259Arg
  • NP_056451.3:p.Cys464Arg
  • NP_751945.2:p.Cys485Arg
  • NC_000002.11:g.27587446A>G
  • Q9UI10:p.Cys465Arg
Protein change:
C259R; CYS465ARG
Links:
UniProtKB: Q9UI10#VAR_016843; OMIM: 606687.0005; dbSNP: rs113994038
NCBI 1000 Genomes Browser:
rs113994038
Molecular consequence:
  • NM_001034116.2:c.1393T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318965.2:c.1456T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318966.2:c.1348T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318967.2:c.1300T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318968.2:c.808T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318969.2:c.775T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015636.4:c.1390T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172195.4:c.1453T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Leukoencephalopathy with vanishing white matter 4 (VWM4)
Synonyms:
Leukoencephalopathy with vanishing white matter 4, with or without ovarian failure
Identifiers:
MONDO: MONDO:0957872; MedGen: C5830406; OMIM: 620314

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000024508OMIM
no assertion criteria provided
Pathogenic
(Jun 1, 2003) 		germlineliterature only

Fogli, A., Rodriguez, D., Eymard-Pierre, E., Bouhour, F., Labauge, P., Meaney, B. F., Zeesman, S., Kaneski, C. R., Schiffmann, R., Boespflug-Tanguy, O. Ovarian failure related to eukaryotic initiation factor 2B mutations. Am. J. Hum. Genet. 72: 1544-1550, 2003.

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Details of each submission

From OMIM, SCV000024508.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature onlynot provided

Description

In 2 sisters (941-1 and 941-2) with vanishing white matter leukodystrophy and ovarian failure (VWM4; 620314), Fogli et al. (2003) found compound heterozygosity for a c.1393C-T transition in the EIF2B4 gene, resulting in a cys465-to-arg (C465R) mutation, and a c.1465C-T transition resulting in a tyr489-to-his mutation (Y489H; 606687.0006). They were examined at 23 and 24 years of age, respectively. Both had had difficulties in school. In both there was spasticity of gait and gait instability having begun at ages 10 and 15 years, respectively; 1 required the use of a walker at age 16 years. Optic atrophy was present in both. Cognitive function was mildly to moderately reduced.

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

Last Updated: Oct 26, 2024