NM_002677.5(PMP2):c.155T>C (p.Ile52Thr) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 21, 2021
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:: RCV001267025.4

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)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001445206	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jul 21, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 26828946, 27009151, 28747762, 30249361 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001445206

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jul 21, 2021)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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

A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy.

Hong YB, Joo J, Hyun YS, Kwak G, Choi YR, Yeo HK, Jwa DH, Kim EJ, Mo WM, Nam SH, Kim SM, Yoo JH, Koo H, Park HT, Chung KW, Choi BO.

PLoS Genet. 2016 Feb;12(2):e1005829. doi: 10.1371/journal.pgen.1005829.

PubMed [citation]

PMID:: 26828946
PMCID:: PMC4735456

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

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV001445206.4

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

Description

The c.155T>C (p.I52T) alteration is located in coding exon 2 of the PMP2 gene. This alteration results from a T to C substitution at nucleotide position 155, causing the isoleucine (I) at amino acid position 52 to be replaced by a threonine (T). Based on data from the Genome Aggregation Database (gnomAD), the PMP2 c.155T>C alteration was not observed, with coverage at this position. This alteration has been detected in multiple individuals with Charcot-Marie-Tooth (CMT) disease type 1 and has been found to co-segregate with disease in different families (Motley, 2016; Punetha, 2018). The p.I52 amino acid is located in the highly-conserved ligand-binding core domain of PMP2 (Hong, 2016; Motley, 2016). Functional analysis showed the p.I52T alteration affects protein aggregation tendency and dynamics (Ruskamo, 2017). The p.I52T alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, this alteration is classified as likely 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: May 7, 2024

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