NM_000304.4(PMP22):c.447C>A (p.Ser149Arg) AND not provided

Clinical significance:Pathogenic (Last evaluated: Oct 18, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000213954.2

Allele description [Variation Report for NM_000304.4(PMP22):c.447C>A (p.Ser149Arg)]

NM_000304.4(PMP22):c.447C>A (p.Ser149Arg)

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.447C>A (p.Ser149Arg)
HGVS:
  • NC_000017.11:g.15230953G>T
  • NG_007949.1:g.39375C>A
  • NM_000304.4:c.447C>AMANE SELECT
  • NM_001281455.2:c.447C>A
  • NM_001281456.2:c.447C>A
  • NM_153321.3:c.447C>A
  • NM_153322.3:c.447C>A
  • NP_000295.1:p.Ser149Arg
  • NP_001268384.1:p.Ser149Arg
  • NP_001268385.1:p.Ser149Arg
  • NP_696996.1:p.Ser149Arg
  • NP_696997.1:p.Ser149Arg
  • LRG_263t1:c.447C>A
  • LRG_263:g.39375C>A
  • NC_000017.10:g.15134270G>T
  • NM_000304.2:c.447C>A
  • NM_000304.3:c.447C>A
  • NM_153322.1:c.447C>A
  • NR_104017.2:n.542C>A
  • NR_104018.2:n.442C>A
  • Q01453:p.Ser149Arg
Protein change:
S149R
Links:
UniProtKB: Q01453#VAR_029970; dbSNP: rs775019409
NCBI 1000 Genomes Browser:
rs775019409
Molecular consequence:
  • NM_000304.4:c.447C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281455.2:c.447C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281456.2:c.447C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153321.3:c.447C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153322.3:c.447C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_104017.2:n.542C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_104018.2:n.442C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000279563GeneDxcriteria provided, single submitter
Pathogenic
(Oct 18, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000279563.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The S149R pathogenic variant in the PMP22 gene has been reported previously as a de novo pathogenic variant in an individual with a clinical diagnosis of Dejerine-Sottas disease (Ohnishi et al., 2000). The S149R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S149R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a conserved position predicted to be within the fourth transmembrane domain of the PMP22 protein (Ohnishi et al., 2000). Missense variants in nearby residues (L147R, G150C/D/R) have been reported in the Human Gene Mutation Database in association with PMP22-related disorders (Stenson et al., 2014). In silico analysis predicts this variant is probably damaging to the protein structure/function.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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