NM_002677.5(PMP2):c.155T>C (p.Ile52Thr) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 19, 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:: RCV002535440.3

Allele description [Variation Report for NM_002677.5(PMP2):c.155T>C (p.Ile52Thr)]

NM_002677.5(PMP2):c.155T>C (p.Ile52Thr)

Gene:

PMP2:peripheral myelin protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q21.13

Genomic location:

Preferred name:

NM_002677.5(PMP2):c.155T>C (p.Ile52Thr)

HGVS:

NC_000008.11:g.81444908A>G
NG_052979.1:g.7616T>C
NM_001348381.2:c.74-307T>C
NM_002677.5:c.155T>CMANE SELECT
NP_002668.1:p.Ile52Thr
NC_000008.10:g.82357143A>G
NM_002677.3:c.155T>C

Protein change:

I52T; ILE52THR

Links:

OMIM: 170715.0002; dbSNP: rs1563518388

NCBI 1000 Genomes Browser:

rs1563518388

Molecular consequence:

NM_001348381.2:c.74-307T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_002677.5:c.155T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003440895	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 19, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27009151, 30249361, 28747762, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003440895

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 19, 2023)

germline

clinical testing

PubMed (4)
[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

De novo PMP2 mutations in families with type 1 Charcot-Marie-Tooth disease.

Motley WW, Palaima P, Yum SW, Gonzalez MA, Tao F, Wanschitz JV, Strickland AV, Löscher WN, De Vriendt E, Koppi S, Medne L, Janecke AR, Jordanova A, Zuchner S, Scherer SS.

Brain. 2016 Jun;139(Pt 6):1649-56. doi: 10.1093/brain/aww055. Epub 2016 Mar 23.

PubMed [citation]

PMID:: 27009151
PMCID:: PMC5022672

Identification of a pathogenic PMP2 variant in a multi-generational family with CMT type 1: Clinical gene panels versus genome-wide approaches to molecular diagnosis.

Punetha J, Mackay-Loder L, Harel T, Coban-Akdemir Z, Jhangiani SN, Gibbs RA, Lee I, Terespolsky D, Lupski JR, Posey JE.

Mol Genet Metab. 2018 Nov;125(3):302-304. doi: 10.1016/j.ymgme.2018.08.005. Epub 2018 Aug 24.

PubMed [citation]

PMID:: 30249361
PMCID:: PMC6326168

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003440895.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 52 of the PMP2 protein (p.Ile52Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 27009151, 30249361). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 599406). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects PMP2 function (PMID: 28747762). For these reasons, this variant has been classified as Pathogenic.

#	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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