NM_003907.3(EIF2B5):c.806G>A (p.Arg269Gln) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 14, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001212143.7

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)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001383719	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 14, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 16864840, 19158808, 27779215, 29933199, 15136673, 15776425, 28492532
SCV001447596	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001383719

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 14, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV001447596

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 23, 2020)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Peripheral neuropathy in vanishing white matter disease with a novel EIF2B5 mutation.

Federico A, Scali O, Stromillo ML, Di Perri C, Bianchi S, Sicurelli F, De Stefano N, Malandrini A, Dotti MT.

Neurology. 2006 Jul 25;67(2):353-5.

PubMed [citation]

PMID:: 16864840

Identification of novel EIF2B mutations in Chinese patients with vanishing white matter disease.

Wu Y, Pan Y, Du L, Wang J, Gu Q, Gao Z, Li J, Leng X, Qin J, Wu X, Jiang Y.

J Hum Genet. 2009 Feb;54(2):74-7. doi: 10.1038/jhg.2008.10. Epub 2009 Jan 16.

PubMed [citation]

PMID:: 19158808

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV001383719.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 269 of the EIF2B5 protein (p.Arg269Gln). This variant is present in population databases (rs113994057, gnomAD 0.0009%). This missense change has been observed in individuals with vanishing white matter disease (PMID: 16864840, 19158808, 27779215, 29933199). ClinVar contains an entry for this variant (Variation ID: 942204). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 (PMID: 15136673, 15776425), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001447596.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 15, 2024

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