NM_000399.5(EGR2):c.1284C>A (p.Ser428Arg) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 16, 2023
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:: RCV001994908.6

Allele description [Variation Report for NM_000399.5(EGR2):c.1284C>A (p.Ser428Arg)]

NM_000399.5(EGR2):c.1284C>A (p.Ser428Arg)

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.1284C>A (p.Ser428Arg)

HGVS:

NC_000010.11:g.62813354G>T
NG_008936.2:g.111547C>A
NM_000399.5:c.1284C>AMANE SELECT
NM_001136177.3:c.1284C>A
NM_001136178.2:c.1284C>A
NM_001136179.3:c.1134C>A
NM_001321037.2:c.1134C>A
NP_000390.2:p.Ser428Arg
NP_001129649.1:p.Ser428Arg
NP_001129650.1:p.Ser428Arg
NP_001129651.1:p.Ser378Arg
NP_001307966.1:p.Ser378Arg
LRG_239:g.111547C>A
NC_000010.10:g.64573114G>T

Protein change:

S378R

Links:

dbSNP: rs754485850

NCBI 1000 Genomes Browser:

rs754485850

Molecular consequence:

NM_000399.5:c.1284C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001136177.3:c.1284C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001136178.2:c.1284C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001136179.3:c.1134C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001321037.2:c.1134C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Charcot-Marie-Tooth disease, type I (CMT1)
Synonyms:: Charcot-Marie-Tooth Neuropathy Type 1; Hereditary Motor and Sensory Neuropathy 1; Charcot-Marie-Tooth, Type 1
Identifiers:: MONDO: MONDO:0019011; MedGen: C0751036

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002244148	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 16, 2023)	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

SCV002244148

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 16, 2023)

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, SCV002244148.3

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

Description

This variant is present in population databases (rs754485850, gnomAD 0.0009%). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EGR2 protein function. ClinVar contains an entry for this variant (Variation ID: 1462789). This variant has not been reported in the literature in individuals affected with EGR2-related conditions. This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 428 of the EGR2 protein (p.Ser428Arg).

#	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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