NM_000399.5(EGR2):c.460A>G (p.Met154Val) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 17, 2019
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:: RCV001219768.6

Allele description [Variation Report for NM_000399.5(EGR2):c.460A>G (p.Met154Val)]

NM_000399.5(EGR2):c.460A>G (p.Met154Val)

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.460A>G (p.Met154Val)

HGVS:

NC_000010.11:g.62814178T>C
NG_008936.2:g.110723A>G
NM_000399.5:c.460A>GMANE SELECT
NM_001136177.3:c.460A>G
NM_001136178.2:c.460A>G
NM_001136179.3:c.310A>G
NM_001321037.2:c.310A>G
NP_000390.2:p.Met154Val
NP_001129649.1:p.Met154Val
NP_001129650.1:p.Met154Val
NP_001129651.1:p.Met104Val
NP_001307966.1:p.Met104Val
LRG_239t1:c.460A>G
LRG_239:g.110723A>G
NC_000010.10:g.64573938T>C
NM_000399.3:c.460A>G

Protein change:

M104V

Links:

dbSNP: rs757301326

NCBI 1000 Genomes Browser:

rs757301326

Molecular consequence:

NM_000399.5:c.460A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001136177.3:c.460A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001136178.2:c.460A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001136179.3:c.310A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001321037.2:c.310A>G - 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

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Microcitrus inodora voucher PI 539741 ribosomal protein S16 (rps16) gene, intron...
Microcitrus inodora voucher PI 539741 ribosomal protein S16 (rps16) gene, intron; chloroplast
gi|123325801|gb|EF126621.1|

Nucleotide
Microcitrus inodora voucher PI 539741 tRNA-Leu (trnL) gene, partial sequence; tr...
Microcitrus inodora voucher PI 539741 tRNA-Leu (trnL) gene, partial sequence; trnL-trnF intergenic spacer, complete sequence; and tRNA-Phe (trnF) gene, partial sequence; chloroplast
gi|123325928|gb|EF126688.1|

Nucleotide
Citrus inodora isolate:PI 539741
Citrus inodora isolate:PI 539741
Citrus inodora primary haplotype genome assembly

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001391723	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 17, 2019)	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

SCV001391723

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 17, 2019)

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, SCV001391723.4

#	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with EGR2-related conditions. This variant is present in population databases (rs757301326, ExAC 0.001%). This sequence change replaces methionine with valine at codon 154 of the EGR2 protein (p.Met154Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine.

#	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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