NM_003907.3(EIF2B5):c.820C>T (p.Arg274Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 28, 2021
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:: RCV001822160.7

Allele description [Variation Report for NM_003907.3(EIF2B5):c.820C>T (p.Arg274Ter)]

NM_003907.3(EIF2B5):c.820C>T (p.Arg274Ter)

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.820C>T (p.Arg274Ter)

HGVS:

NC_000003.12:g.184140134C>T
NG_015826.1:g.10113C>T
NM_003907.3:c.820C>TMANE SELECT
NP_003898.2:p.Arg274Ter
LRG_1278t1:c.820C>T
LRG_1278:g.10113C>T
LRG_1278p1:p.Arg274Ter
NC_000003.11:g.183857922C>T
NM_003907.2:c.820C>T

Protein change:

R274*

Links:

dbSNP: rs1334515681

NCBI 1000 Genomes Browser:

rs1334515681

Molecular consequence:

NM_003907.3:c.820C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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poly(3-hydroxybutyrate) depolymerase [Burkholderia pseudomallei]
poly(3-hydroxybutyrate) depolymerase [Burkholderia pseudomallei]
gi|2617925911|emb|CAK1301601.1||gnl CIGK|CAK1301601

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002064511	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 31, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002226120	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 28, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11704758, 15060152, 21307862, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002064511

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 31, 2017)

germline

clinical testing

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

SCV002226120

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 28, 2021)

germline

clinical testing

PubMed (4)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

Subunits of the translation initiation factor eIF2B are mutant in leukoencephalopathy with vanishing white matter.

Leegwater PA, Vermeulen G, Könst AA, Naidu S, Mulders J, Visser A, Kersbergen P, Mobach D, Fonds D, van Berkel CG, Lemmers RJ, Frants RR, Oudejans CB, Schutgens RB, Pronk JC, van der Knaap MS.

Nat Genet. 2001 Dec;29(4):383-8.

PubMed [citation]

PMID:: 11704758

See all PubMed Citations (5)

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV002064511.1

#	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	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV002226120.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with EIF2B5-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg274*) in the EIF2B5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EIF2B5 are known to be pathogenic (PMID: 11704758, 15060152, 21307862).

#	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 20, 2024

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