NM_005670.4(EPM2A):c.86T>C (p.Leu29Pro) AND Progressive myoclonic epilepsy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 12, 2021
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:: RCV001957672.6

Allele description [Variation Report for NM_005670.4(EPM2A):c.86T>C (p.Leu29Pro)]

NM_005670.4(EPM2A):c.86T>C (p.Leu29Pro)

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.86T>C (p.Leu29Pro)

HGVS:

NC_000006.12:g.145735413A>G
NG_012832.2:g.5443T>C
NM_001018041.2:c.86T>C
NM_001360057.2:c.86T>C
NM_001360064.2:c.-114+495T>C
NM_001360071.2:c.-584T>C
NM_001368129.2:c.-538T>C
NM_001368130.1:c.86T>C
NM_001368131.1:c.-282T>C
NM_005670.3:c.86T>C
NM_005670.4:c.86T>CMANE SELECT
NP_001018051.1:p.Leu29Pro
NP_001346986.1:p.Leu29Pro
NP_001355059.1:p.Leu29Pro
NP_005661.1:p.Leu29Pro
NC_000006.11:g.146056549A>G

Protein change:

L29P

Links:

dbSNP: rs2128649883

NCBI 1000 Genomes Browser:

rs2128649883

Molecular consequence:

NM_001360071.2:c.-584T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001368129.2:c.-538T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001368131.1:c.-282T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001360064.2:c.-114+495T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001018041.2:c.86T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001360057.2:c.86T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001368130.1:c.86T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005670.4:c.86T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002212975	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 12, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002212975

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 12, 2021)

germline

clinical testing

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

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

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002212975.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Leu29 amino acid residue in EPM2A. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with EPM2A-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces leucine with proline at codon 29 of the EPM2A protein (p.Leu29Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline.

#	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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