NM_003907.3(EIF2B5):c.3G>C (p.Met1Ile) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 11, 2020
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:: RCV001378649.6

Allele description

NM_003907.3(EIF2B5):c.3G>C (p.Met1Ile)

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.3G>C (p.Met1Ile)

HGVS:

NC_000003.12:g.184135388G>C
NG_015826.1:g.5367G>C
NM_003907.3:c.3G>CMANE SELECT
NP_003898.2:p.Met1Ile
LRG_1278t1:c.3G>C
LRG_1278:g.5367G>C
LRG_1278p1:p.Met1Ile
NC_000003.11:g.183853176G>C

Protein change:

M1I

Links:

dbSNP: rs2109005483

NCBI 1000 Genomes Browser:

rs2109005483

Molecular consequence:

NM_003907.3:c.3G>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_003907.3:c.3G>C - 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
SCV001576265	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Feb 11, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15136673, 27665184, 15054402, 18263758, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001576265

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Feb 11, 2020)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

The effect of genotype on the natural history of eIF2B-related leukodystrophies.

Fogli A, Schiffmann R, Bertini E, Ughetto S, Combes P, Eymard-Pierre E, Kaneski CR, Pineda M, Troncoso M, Uziel G, Surtees R, Pugin D, Chaunu MP, Rodriguez D, Boespflug-Tanguy O.

Neurology. 2004 May 11;62(9):1509-17.

PubMed [citation]

PMID:: 15136673

An unusual neuroimaging finding and response to immunotherapy in a child with genetically confirmed vanishing white matter disease.

Singh RR, Livingston J, Lim M, Berry IR, Siddiqui A.

Eur J Paediatr Neurol. 2017 Mar;21(2):410-413. doi: 10.1016/j.ejpn.2016.08.012. Epub 2016 Sep 6.

PubMed [citation]

PMID:: 27665184

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001576265.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant has not been reported in the literature in individuals with EIF2B5-related conditions. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Glu81 amino acid residue in EIF2B5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15136673, 27665184, 15054402, 18263758). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant is not present in population databases (ExAC no frequency). This sequence change affects the initiator methionine of the EIF2B5 mRNA. The next in-frame methionine is located at codon 181.

#	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

Last Updated: Feb 28, 2024

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