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NM_000399.5(EGR2):c.736C>T (p.Arg246Cys) AND Charcot-Marie-Tooth disease, type I

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 19, 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:
RCV001997184.6

Allele description [Variation Report for NM_000399.5(EGR2):c.736C>T (p.Arg246Cys)]

NM_000399.5(EGR2):c.736C>T (p.Arg246Cys)

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.736C>T (p.Arg246Cys)
HGVS:
  • NC_000010.11:g.62813902G>A
  • NG_008936.2:g.110999C>T
  • NM_000399.5:c.736C>TMANE SELECT
  • NM_001136177.3:c.736C>T
  • NM_001136178.2:c.736C>T
  • NM_001136179.3:c.586C>T
  • NM_001321037.2:c.586C>T
  • NP_000390.2:p.Arg246Cys
  • NP_001129649.1:p.Arg246Cys
  • NP_001129650.1:p.Arg246Cys
  • NP_001129651.1:p.Arg196Cys
  • NP_001307966.1:p.Arg196Cys
  • LRG_239t1:c.736C>T
  • LRG_239:g.110999C>T
  • NC_000010.10:g.64573662G>A
  • NM_000399.3:c.736C>T
Protein change:
R196C
Links:
dbSNP: rs774391305
NCBI 1000 Genomes Browser:
rs774391305
Molecular consequence:
  • NM_000399.5:c.736C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001136177.3:c.736C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001136178.2:c.736C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001136179.3:c.586C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001321037.2:c.586C>T - 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

Recent activity

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002234909Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 19, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Charcot-Marie-Tooth disease with pyramidal features due to a new mutation of EGR2 gene.

Fusco C, Spagnoli C, Salerno GG, Pavlidis E, Frattini D, Pisani F, Bassi MT.

Acta Biomed. 2019 Jan 24;90(1):104-107. doi: 10.23750/abm.v90i1.6951.

PubMed [citation]
PMID:
30889162
PMCID:
PMC6502152

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, SCV002234909.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on EGR2 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 1448653). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 30889162). This variant is present in population databases (rs774391305, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 246 of the EGR2 protein (p.Arg246Cys).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024