NM_000399.5(EGR2):c.947C>T (p.Pro316Leu) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 20, 2018
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:: RCV000806454.6

Allele description [Variation Report for NM_000399.5(EGR2):c.947C>T (p.Pro316Leu)]

NM_000399.5(EGR2):c.947C>T (p.Pro316Leu)

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.947C>T (p.Pro316Leu)

HGVS:

NC_000010.11:g.62813691G>A
NG_008936.2:g.111210C>T
NM_000399.5:c.947C>TMANE SELECT
NM_001136177.3:c.947C>T
NM_001136178.2:c.947C>T
NM_001136179.3:c.797C>T
NM_001321037.2:c.797C>T
NP_000390.2:p.Pro316Leu
NP_001129649.1:p.Pro316Leu
NP_001129650.1:p.Pro316Leu
NP_001129651.1:p.Pro266Leu
NP_001307966.1:p.Pro266Leu
LRG_239t1:c.947C>T
LRG_239:g.111210C>T
NC_000010.10:g.64573451G>A
NM_000399.3:c.947C>T

Protein change:

P266L

Links:

dbSNP: rs1589080747

NCBI 1000 Genomes Browser:

rs1589080747

Molecular consequence:

NM_000399.5:c.947C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001136177.3:c.947C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001136178.2:c.947C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001136179.3:c.797C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001321037.2:c.797C>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000946456	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 20, 2018)	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

SCV000946456

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 20, 2018)

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, SCV000946456.3

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

Description

This sequence change replaces proline with leucine at codon 316 of the EGR2 protein (p.Pro316Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with EGR2-related disease. This variant is not present in population databases (ExAC no frequency).

#	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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