NM_000399.5(EGR2):c.910GCC[7] (p.Ala309dup) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 6, 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:: RCV000546559.8

Allele description [Variation Report for NM_000399.5(EGR2):c.910GCC[7] (p.Ala309dup)]

NM_000399.5(EGR2):c.910GCC[7] (p.Ala309dup)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

10q21.3

Genomic location:

Preferred name:

NM_000399.5(EGR2):c.910GCC[7] (p.Ala309dup)

HGVS:

NC_000010.11:g.62813711GGC[7]
NG_008936.2:g.111173GCC[7]
NM_000399.5:c.910GCC[7]MANE SELECT
NM_001136177.3:c.910GCC[7]
NM_001136178.2:c.910GCC[7]
NM_001136179.3:c.760GCC[7]
NM_001321037.2:c.760GCC[7]
NP_000390.2:p.Ala309dup
NP_001129649.1:p.Ala309dup
NP_001129650.1:p.Ala309dup
NP_001129651.1:p.Ala259dup
NP_001307966.1:p.Ala259dup
LRG_239t1:c.925_927dup
LRG_239:g.111173GCC[7]
NC_000010.10:g.64573470_64573471insGGC
NC_000010.10:g.64573471GGC[7]
NM_000399.3:c.925_927dup
NM_000399.3:c.925_927dupGCC
NM_000399.4:c.925_927dup
NM_000399.5:c.925_927dupMANE SELECT

Links:

dbSNP: rs753747037

NCBI 1000 Genomes Browser:

rs753747037

Molecular consequence:

NM_000399.5:c.910GCC[7] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001136177.3:c.910GCC[7] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001136178.2:c.910GCC[7] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001136179.3:c.760GCC[7] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001321037.2:c.760GCC[7] - inframe_insertion - [Sequence Ontology: SO:0001821]

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
SCV000636236	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 6, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32376792, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000636236

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 6, 2023)

germline

clinical testing

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

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

Comprehensive genetic sequence and copy number analysis for Charcot-Marie-Tooth disease in a Canadian cohort of 2517 patients.

Volodarsky M, Kerkhof J, Stuart A, Levy M, Brady LI, Tarnopolsky M, Lin H, Ainsworth P, Sadikovic B.

J Med Genet. 2021 Apr;58(4):284-288. doi: 10.1136/jmedgenet-2019-106641. Epub 2020 May 6.

PubMed [citation]

PMID:: 32376792

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 Invitae, SCV000636236.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant, c.925_927dup, results in the insertion of 1 amino acid(s) of the EGR2 protein (p.Ala309dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs753747037, gnomAD 0.03%). This variant has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 418176). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.

#	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: May 7, 2024

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