NM_000304.4(PMP22):c.185T>G (p.Leu62Arg) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 19, 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:: RCV001194158.1

Allele description [Variation Report for NM_000304.4(PMP22):c.185T>G (p.Leu62Arg)]

NM_000304.4(PMP22):c.185T>G (p.Leu62Arg)

Gene:

PMP22:peripheral myelin protein 22 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p12

Genomic location:

Preferred name:

NM_000304.4(PMP22):c.185T>G (p.Leu62Arg)

HGVS:

NC_000017.11:g.15239605A>C
NG_007949.1:g.30723T>G
NM_000304.4:c.185T>GMANE SELECT
NM_001281455.2:c.185T>G
NM_001281456.2:c.185T>G
NM_001330143.2:c.185T>G
NM_153321.3:c.185T>G
NM_153322.3:c.185T>G
NP_000295.1:p.Leu62Arg
NP_001268384.1:p.Leu62Arg
NP_001268385.1:p.Leu62Arg
NP_001317072.1:p.Leu62Arg
NP_696996.1:p.Leu62Arg
NP_696997.1:p.Leu62Arg
LRG_263t1:c.185T>G
LRG_263:g.30723T>G
NC_000017.10:g.15142922A>C
NM_000304.2:c.185T>G
NM_000304.3:c.185T>G
NR_104017.2:n.280T>G
NR_104018.2:n.180T>G

Protein change:

L62R

Links:

dbSNP: rs756046682

NCBI 1000 Genomes Browser:

rs756046682

Molecular consequence:

NM_000304.4:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281455.2:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281456.2:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330143.2:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_153321.3:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_153322.3:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_104017.2:n.280T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104018.2:n.180T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001363467	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Dec 19, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001363467

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Dec 19, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Application of targeted multi-gene panel testing for the diagnosis of inherited peripheral neuropathy provides a high diagnostic yield with unexpected phenotype-genotype variability.

Antoniadi T, Buxton C, Dennis G, Forrester N, Smith D, Lunt P, Burton-Jones S.

BMC Med Genet. 2015 Sep 21;16:84. doi: 10.1186/s12881-015-0224-8.

PubMed [citation]

PMID:: 26392352
PMCID:: PMC4578331

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363467.1

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

Description

Variant summary: PMP22 c.185T>G (p.Leu62Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251160 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.185T>G has been reported in the literature in an individual affected with hereditary motor neuropathy (Antoniadi_2015). This report does not provide unequivocal conclusions about association of the variant with PMP22-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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: Sep 29, 2024

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