NM_000399.5(EGR2):c.1232A>G (p.Asp411Gly) AND Dejerine-Sottas disease

Germline classification:: Pathogenic (1 submission)
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:: RCV002051605.2

Allele description [Variation Report for NM_000399.5(EGR2):c.1232A>G (p.Asp411Gly)]

NM_000399.5(EGR2):c.1232A>G (p.Asp411Gly)

Gene:

EGR2:early growth response 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q21.3

Genomic location:

Preferred name:

NM_000399.5(EGR2):c.1232A>G (p.Asp411Gly)

HGVS:

NC_000010.11:g.62813406T>C
NG_008936.2:g.111495A>G
NM_000399.5:c.1232A>GMANE SELECT
NM_001136177.3:c.1232A>G
NM_001136178.2:c.1232A>G
NM_001136179.3:c.1082A>G
NM_001321037.2:c.1082A>G
NP_000390.2:p.Asp411Gly
NP_001129649.1:p.Asp411Gly
NP_001129650.1:p.Asp411Gly
NP_001129651.1:p.Asp361Gly
NP_001307966.1:p.Asp361Gly
LRG_239:g.111495A>G
NC_000010.10:g.64573166T>C

Protein change:

D361G

Links:

dbSNP: rs2132702182

NCBI 1000 Genomes Browser:

rs2132702182

Molecular consequence:

NM_000399.5:c.1232A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001136177.3:c.1232A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001136178.2:c.1232A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001136179.3:c.1082A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001321037.2:c.1082A>G - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Decreased function

Condition(s)

Name:: Dejerine-Sottas disease
Synonyms:: HEREDITARY MOTOR AND SENSORY NEUROPATHY TYPE III; HMSN Type III; Hypertrophic neuropathy of Dejerine-Sottas; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007790; MedGen: C0011195; Orphanet: 64748; OMIM: 145900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002107181	Northcott Neuroscience Laboratory, ANZAC Research Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	de novo	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

SCV002107181

Northcott Neuroscience Laboratory, ANZAC Research Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

de novo

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	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Northcott Neuroscience Laboratory, ANZAC Research Institute, SCV002107181.1

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

Description

The sporadic de novo EGR2 variant, c.1232A > G (NM_000399.5), causes a missense p.Asp411Gly substitution and was discovered through whole-exome sequencing (WES) of the proband. The resultant phenotype is severe demyelinating DSN with onset at two years of age, confirmed through nerve biopsy and electrophysiological examination. In silico analyses showed that the Asp411 residue is evolutionarily conserved, and the p.Asp411Gly variant was predicted to be deleterious by multiple in silico analyses. A luciferase-based reporter assay confirmed the reduced ability of p.Asp411Gly EGR2 to activate a PMP22 (peripheral myelin protein 22) enhancer element compared to wild-type EGR2. (https://doi.org/10.1038/s41598-019-55875-4)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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