NM_004836.7(EIF2AK3):c.3141T>A (p.Tyr1047Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 12, 2023
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:: RCV003574078.2

Allele description [Variation Report for NM_004836.7(EIF2AK3):c.3141T>A (p.Tyr1047Ter)]

NM_004836.7(EIF2AK3):c.3141T>A (p.Tyr1047Ter)

Genes:

EIF2AK3:eukaryotic translation initiation factor 2 alpha kinase 3 [Gene - OMIM - HGNC]
LOC101928371:uncharacterized LOC101928371 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

2p11.2

Genomic location:

Preferred name:

NM_004836.7(EIF2AK3):c.3141T>A (p.Tyr1047Ter)

HGVS:

NC_000002.12:g.88558926A>T
NG_016424.1:g.73651T>A
NM_001313915.2:c.2688T>A
NM_004836.7:c.3141T>AMANE SELECT
NP_001300844.1:p.Tyr896Ter
NP_004827.4:p.Tyr1047Ter
LRG_1024t1:c.3141T>A
LRG_1024:g.73651T>A
LRG_1024p1:p.Tyr1047Ter
NC_000002.11:g.88858444A>T

Protein change:

Y1047*

Molecular consequence:

NM_001313915.2:c.2688T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_004836.7:c.3141T>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV004332222	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 12, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19837917, 24168455, 24710710, 33452782, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004332222

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 12, 2023)

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

Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families.

Rubio-Cabezas O, Patch AM, Minton JA, Flanagan SE, Edghill EL, Hussain K, Balafrej A, Deeb A, Buchanan CR, Jefferson IG, Mutair A; Neonatal Diabetes International Collaborative Group, Hattersley AT, Ellard S.

J Clin Endocrinol Metab. 2009 Nov;94(11):4162-70. doi: 10.1210/jc.2009-1137. Epub 2009 Oct 16. Erratum in: J Clin Endocrinol Metab. 2010 Mar;95(3):1480. Tukkahrman, Doga [corrected to Turkkahraman, Doga].

PubMed [citation]

PMID:: 19837917
PMCID:: PMC2775655

EIF2AK3 mutations in South Indian children with permanent neonatal diabetes mellitus associated with Wolcott-Rallison syndrome.

Jahnavi S, Poovazhagi V, Kanthimathi S, Gayathri V, Mohan V, Radha V.

Pediatr Diabetes. 2014 Jun;15(4):313-8. doi: 10.1111/pedi.12089. Epub 2013 Oct 30.

PubMed [citation]

PMID:: 24168455

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004332222.1

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

Description

This sequence change creates a premature translational stop signal (p.Tyr1047*) in the EIF2AK3 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 70 amino acid(s) of the EIF2AK3 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EIF2AK3-related conditions. This variant disrupts a region of the EIF2AK3 protein in which other variant(s) (p.Arg1065*) have been determined to be pathogenic (PMID: 19837917, 24168455, 24710710, 33452782). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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

Last Updated: Sep 29, 2024

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