EPM2A

EPM2A glucan phosphatase, laforin, the group of Atypical dual specificity phosphatases

Basic information

Region (hg38): 6:145382534-145736023

Links

ENSG00000112425 ∙ NCBI:7957 ∙ OMIM:607566 ∙ HGNC:3413 ∙ Uniprot:B3EWF7, O95278 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Lafora disease (Strong), mode of inheritance: AR
• Lafora disease (Strong), mode of inheritance: AR
• Lafora disease (Strong), mode of inheritance: AR
• Lafora disease (Supportive), mode of inheritance: AR
• Lafora disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, progressive myoclonic 2A (Lafora)	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	9771710; 10513696; 14663053; 15277643; 16157917; 16356781; 20301563
Some antiepileptic drugs may be effective, but certain medications (eg, phenytoin, and possibly carbamazepine, oxcarbazepine, and lamotrigine) can exacerbate myoclonus

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPM2A gene.

• Progressive myoclonic epilepsy (314 variants)
• not provided (109 variants)
• Inborn genetic diseases (67 variants)
• not specified (39 variants)
• Lafora disease (25 variants)
• Seizure (3 variants)
• Microcephaly;Cataract;Severe global developmental delay (1 variants)
• Abnormality of the nervous system (1 variants)
• Intellectual disability (1 variants)
• Myoclonic epilepsy, progressive, X-linked (1 variants)
• Severe global developmental delay;Cataract;Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPM2A 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	75	2	79
missense	3	6	184	21	1	215
nonsense	7	4	1	1		13
start loss	1					1
frameshift	9	2				11
inframe indel		1	5			6
splice donor/acceptor (+/-2bp)	3	1	1			5
splice region			2	5	1	8
non coding	1		3	24	11	39
Total	24	14	196	121	14

Highest pathogenic variant AF is 0.0000591

Variants in EPM2A

This is a list of pathogenic ClinVar variants found in the EPM2A region.

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

Position	Type	Phenotype	Significance	ClinVar
6-145625446-A-G			Likely benign (Jun 26, 2018)
6-145625685-C-T		EPM2A-related disorder	Likely benign (Sep 09, 2019)
6-145625712-C-T			Uncertain significance (Apr 01, 2024)
6-145625724-CCT-C			Likely benign (May 26, 2017)
6-145625725-C-T		Severe global developmental delay;Cataract;Microcephaly	Uncertain significance (Jan 01, 2017)
6-145625777-G-A			Benign (Jun 26, 2018)
6-145625944-C-T			Benign (Jun 14, 2018)
6-145627244-T-C			Likely benign (Jul 05, 2018)
6-145627253-A-C			Benign (Jun 26, 2018)
6-145627403-GCAGGCTGACCAGCTA-G		Progressive myoclonic epilepsy	Uncertain significance (May 04, 2022)
6-145627420-A-G			Uncertain significance (Jan 09, 2015)
6-145627423-C-A			Uncertain significance (Dec 03, 2019)
6-145627426-C-T		Progressive myoclonic epilepsy	Uncertain significance (Nov 27, 2018)
6-145627428-C-A		Progressive myoclonic epilepsy	Likely benign (Nov 05, 2022)
6-145627431-A-C		Progressive myoclonic epilepsy	Uncertain significance (Dec 02, 2021)
6-145627433-A-G		Progressive myoclonic epilepsy	Uncertain significance (Apr 24, 2020)
6-145627435-G-A		Progressive myoclonic epilepsy	Uncertain significance (Sep 28, 2019)
6-145627437-A-G		Progressive myoclonic epilepsy	Likely benign (Nov 04, 2023)
6-145627438-C-T		not specified • Progressive myoclonic epilepsy	Conflicting classifications of pathogenicity (Jun 24, 2021)
6-145627439-G-A		Progressive myoclonic epilepsy	Uncertain significance (Nov 20, 2019)
6-145627442-C-A		Progressive myoclonic epilepsy	Uncertain significance (Jun 16, 2022)
6-145627450-A-C		Progressive myoclonic epilepsy	Uncertain significance (Mar 25, 2021)
6-145627455-C-G		Progressive myoclonic epilepsy	Uncertain significance (Mar 18, 2022)
6-145627458-G-GA		Lafora disease	Pathogenic (Oct 01, 2005)
6-145627470-T-C		Progressive myoclonic epilepsy	Likely benign (Sep 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPM2A	protein_coding	protein_coding	ENST00000367519	4	234442

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000872	0.545	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.260	165	156	1.06	0.00000893	2124
Missense in Polyphen		64	59.944	1.0677		676
Synonymous	-1.64	78	61.6	1.27	0.00000373	660
Loss of Function	0.733	9	11.7	0.769	5.89e-7	141

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000265	0.000264
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000223	0.000220
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Pathway: Metabolism of carbohydrates;Metabolism;Glycogen synthesis;Glycogen metabolism (Consensus)

Recessive Scores

• pRec: 0.325

Haploinsufficiency Scores

• pHI: 0.549
• hipred: Y
• hipred_score: 0.728
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.675

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Epm2a
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; muscle phenotype; neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; immune system phenotype

Gene ontology

• Biological process: positive regulation of macroautophagy;negative regulation of TOR signaling
• Cellular component: nucleus
• Molecular function: protein binding