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NM_003907.3(EIF2B5):c.806G>A (p.Arg269Gln) AND Leukoencephalopathy with vanishing white matter 1

Germline classification:
Likely pathogenic (1 submission)
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:
RCV003389333.3

Allele description [Variation Report for NM_003907.3(EIF2B5):c.806G>A (p.Arg269Gln)]

NM_003907.3(EIF2B5):c.806G>A (p.Arg269Gln)

Gene:
EIF2B5:eukaryotic translation initiation factor 2B subunit epsilon [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q27.1
Genomic location:
Preferred name:
NM_003907.3(EIF2B5):c.806G>A (p.Arg269Gln)
HGVS:
  • NC_000003.12:g.184140120G>A
  • NG_015826.1:g.10099G>A
  • NM_003907.3:c.806G>AMANE SELECT
  • NP_003898.2:p.Arg269Gln
  • LRG_1278t1:c.806G>A
  • LRG_1278:g.10099G>A
  • LRG_1278p1:p.Arg269Gln
  • NC_000003.11:g.183857908G>A
  • NM_003907.2:c.806G>A
Protein change:
R269Q
Links:
dbSNP: rs113994057
NCBI 1000 Genomes Browser:
rs113994057
Molecular consequence:
  • NM_003907.3:c.806G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Leukoencephalopathy with vanishing white matter 1 (VWM1)
Synonyms:
CHILDHOOD ATAXIA WITH CENTRAL NERVOUS SYSTEM HYPOMYELINIZATION; Cree leukoencephalopathy; Vanishing white matter leukodystrophy
Identifiers:
MONDO: MONDO:0020507; MedGen: C5779972; OMIM: 603896

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004101485Neuberg Centre For Genomic Medicine, NCGM
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenicgermlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV004101485.1

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

Description

The EIF2B5 c.806G>A p.Arg269Gln variant has been reported in individuals affected with vanishing white matter disease (Federico A et al, 2006). This variant disrupts the p.Arg269 amino acid residue in EIF2B5. Other variant(s) that disrupt this residue have been observed in individuals with EIF2B5-related conditions (Fogli et al, 2004), which suggests that this may be a clinically significant amino acid residue. This variant is reported with the allele frequency (0.00039%) in the gnomAD and novel in 1000 genome database. It has been submitted to ClinVar with varying interpretations: Pathogenic/ Likely Pathogenic. The amino acid Arg at position 269 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by PolyPhen2 and the residue is conserved across species. The amino acid change p.Arg269Gln in EIF2B5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.

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

Last Updated: Jul 15, 2024