NM_005670.4(EPM2A):c.96G>A (p.Trp32Ter) AND Progressive myoclonic epilepsy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 17, 2022
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:: RCV002847744.2

Allele description [Variation Report for NM_005670.4(EPM2A):c.96G>A (p.Trp32Ter)]

NM_005670.4(EPM2A):c.96G>A (p.Trp32Ter)

Genes:

LOC129997381:ATAC-STARR-seq lymphoblastoid silent region 17642 [Gene]
EPM2A-DT:EPM2A divergent transcript [Gene - HGNC]
EPM2A:EPM2A glucan phosphatase, laforin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q24.3

Genomic location:

Preferred name:

NM_005670.4(EPM2A):c.96G>A (p.Trp32Ter)

HGVS:

NC_000006.12:g.145735403C>T
NG_012832.2:g.5453G>A
NG_012832.3:g.5620G>A
NM_001018041.2:c.96G>A
NM_001360057.2:c.96G>A
NM_001360064.2:c.-114+505G>A
NM_001360071.2:c.-574G>A
NM_001368129.2:c.-528G>A
NM_001368130.1:c.96G>A
NM_001368131.1:c.-272G>A
NM_005670.4:c.96G>AMANE SELECT
NP_001018051.1:p.Trp32Ter
NP_001346986.1:p.Trp32Ter
NP_001355059.1:p.Trp32Ter
NP_005661.1:p.Trp32Ter
NC_000006.11:g.146056539C>T
NR_153397.1:n.118G>A

Protein change:

W32*

Molecular consequence:

NM_001360071.2:c.-574G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001368129.2:c.-528G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001368131.1:c.-272G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001360064.2:c.-114+505G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001018041.2:c.96G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001360057.2:c.96G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001368130.1:c.96G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_005670.4:c.96G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Progressive myoclonic epilepsy
Synonyms:: Myoclonic Epilepsies, Progressive; Familial progressive myoclonic epilepsy; Progressive myoclonus epilepsy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0020074; MedGen: C0751778; Orphanet: 308; OMIM: PS254800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003229598	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 17, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20738377, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003229598

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 17, 2022)

germline

clinical testing

PubMed (2)
[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

Novel mutations in EPM2A and NHLRC1 widen the spectrum of Lafora disease.

Lesca G, Boutry-Kryza N, de Toffol B, Milh M, Steschenko D, Lemesle-Martin M, Maillard L, Foletti G, Rudolf G, Nielsen JE, á Rogvi-Hansen B, Erdal J, Mancini J, Thauvin-Robinet C, M'Rrabet A, Ville D, Szepetowski P, Raffo E, Hirsch E, Ryvlin P, Calender A, Genton P.

Epilepsia. 2010 Sep;51(9):1691-8. doi: 10.1111/j.1528-1167.2010.02692.x. Epub 2010 Aug 5.

PubMed [citation]

PMID:: 20738377

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003229598.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with EPM2A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp32*) in the EPM2A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EPM2A are known to be pathogenic (PMID: 20738377).

#	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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