EIF2B2

eukaryotic translation initiation factor 2B subunit beta

Basic information

Region (hg38): 14:75002920-75012366

Links

ENSG00000119718 ∙ NCBI:8892 ∙ OMIM:606454 ∙ HGNC:3258 ∙ Uniprot:P49770 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• leukoencephalopathy with vanishing white matter (Definitive), mode of inheritance: AR
• leukoencephalopathy with vanishing white matter (Strong), mode of inheritance: AR
• ovarioleukodystrophy (Supportive), mode of inheritance: AR
• leukoencephalopathy with vanishing white matter 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukoencephalopathy with vanishing white matter 2	AR	Obstetric	Individuals with Ovarioleukodystrophy may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desired	Endocrine; Neurologic; Obstetric	11704758; 11835386; 14566705; 15054402; 18263758; 19625339; 21484434; 22285377; 20301435; 22678813; 22729508
The evidence is unclear, but it is possible that certain circumstances may aggravate the condition and accelerate neurological decline, including head trauma (children may benefit from wearing helmets), contact sports, and stressful situations (including high body temperature, and prophylactic measures and rapid treatment related to infections may be beneficial)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EIF2B2 gene.

• not provided (148 variants)
• Vanishing white matter disease (48 variants)
• Inborn genetic diseases (14 variants)
• Leukoencephalopathy with vanishing white matter 2 (6 variants)
• Lynch syndrome (3 variants)
• Abnormality of the nervous system (2 variants)
• not specified (2 variants)
• Premature ovarian insufficiency (2 variants)
• EIF2B2-related condition (2 variants)
• See cases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EIF2B2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	30	1	33
missense	2	7	56		2	67
nonsense	3	2	1			6
start loss	1	1	1			3
frameshift	4		1			5
inframe indel			2			2
splice donor/acceptor (+/-2bp)		3				3
splice region			2	2		4
non coding			10	19	19	48
Total	10	13	73	49	22

Highest pathogenic variant AF is 0.0000722

Variants in EIF2B2

This is a list of pathogenic ClinVar variants found in the EIF2B2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-75002931-A-G		Vanishing white matter disease	Uncertain significance (Jan 12, 2018)
14-75002935-T-C		Vanishing white matter disease	Uncertain significance (Jan 12, 2018)
14-75002961-C-G		Vanishing white matter disease	Uncertain significance (Jan 12, 2018)
14-75002991-A-G		Vanishing white matter disease	Uncertain significance (Jun 24, 2022)
14-75002993-G-A		Vanishing white matter disease	Likely pathogenic (Feb 20, 2020)
14-75002993-G-T			Pathogenic (Jan 30, 2017)
14-75002995-C-T		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
14-75002996-G-A			Likely benign (Mar 26, 2023)
14-75002999-A-T			Likely benign (Jul 16, 2023)
14-75003002-C-G			Likely benign (Mar 26, 2023)
14-75003005-A-C			Likely benign (Apr 17, 2018)
14-75003006-G-C			Uncertain significance (Sep 02, 2021)
14-75003012-G-A		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
14-75003013-G-C			Uncertain significance (Aug 17, 2021)
14-75003022-T-C		Inborn genetic diseases	Uncertain significance (Jun 07, 2023)
14-75003024-T-C			Uncertain significance (Dec 02, 2021)
14-75003029-G-A			Likely benign (Oct 26, 2023)
14-75003030-AG-A		Vanishing white matter disease	Pathogenic (Feb 20, 2020)
14-75003038-G-A			Likely benign (Mar 07, 2023)
14-75003041-C-T			Likely benign (Dec 01, 2023)
14-75003053-C-T			Likely benign (Apr 19, 2022)
14-75003054-C-T			Benign (Jan 29, 2024)
14-75003056-G-T			Likely benign (Mar 21, 2023)
14-75003062-G-C			Likely benign (Dec 01, 2023)
14-75003066-G-C			Benign (Oct 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EIF2B2	protein_coding	protein_coding	ENST00000266126	8	6679

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.08e-10	0.0706	125686	0	62	125748	0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.03	149	189	0.789	0.00000959	2302
Missense in Polyphen		29	53.132	0.54581		684
Synonymous	-0.129	76	74.6	1.02	0.00000403	709
Loss of Function	0.0416	15	15.2	0.988	8.32e-7	176

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000289	0.000289
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000264	0.000264
Middle Eastern	0.000109	0.000109
South Asian	0.000457	0.000457
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP.
• Disease: DISEASE: Leukodystrophy with vanishing white matter (VWM) [MIM:603896]: A leukodystrophy that occurs mainly in children. Neurological signs include progressive cerebellar ataxia, spasticity, inconstant optic atrophy and relatively preserved mental abilities. The disease is chronic-progressive with, in most individuals, additional episodes of rapid deterioration following febrile infections or minor head trauma. While childhood onset is the most common form of the disorder, some severe forms are apparent at birth. A severe, early-onset form seen among the Cree and Chippewayan populations of Quebec and Manitoba is called Cree leukoencephalopathy. Milder forms may not become evident until adolescence or adulthood. Some females with milder forms of the disease who survive to adolescence exhibit ovarian dysfunction. This variant of the disorder is called ovarioleukodystrophy. {ECO:0000269|PubMed:11704758, ECO:0000269|PubMed:12707859, ECO:0000269|PubMed:15776425, ECO:0000269|PubMed:21484434, ECO:0000269|PubMed:22285377, ECO:0000269|PubMed:22729508}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: RNA transport - Homo sapiens (human);Translation Factors;Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling;Recycling of eIF2:GDP;Eukaryotic Translation Initiation;Translation;Metabolism of proteins;Cap-dependent Translation Initiation (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• loftool: 0.317
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.32

Haploinsufficiency Scores

• pHI: 0.223
• hipred: Y
• hipred_score: 0.751
• ghis: 0.593

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.829

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Eif2b2
• Phenotype: hematopoietic system phenotype

Gene ontology

• Biological process: ovarian follicle development;translational initiation;regulation of translational initiation;central nervous system development;response to heat;response to glucose;oligodendrocyte development;myelination;response to peptide hormone;T cell receptor signaling pathway
• Cellular component: cytoplasm;cytosol;eukaryotic translation initiation factor 2B complex
• Molecular function: translation initiation factor activity;guanyl-nucleotide exchange factor activity;protein binding;ATP binding;GTP binding