NM_000304.4(PMP22):c.449G>A (p.Gly150Asp) AND not provided

Clinical significance:Pathogenic (Last evaluated: Jan 4, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000236879.2

Allele description [Variation Report for NM_000304.4(PMP22):c.449G>A (p.Gly150Asp)]

NM_000304.4(PMP22):c.449G>A (p.Gly150Asp)

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.449G>A (p.Gly150Asp)
HGVS:
  • NC_000017.11:g.15230951C>T
  • NG_007949.1:g.39377G>A
  • NM_000304.4:c.449G>AMANE SELECT
  • NM_001281455.2:c.449G>A
  • NM_001281456.2:c.449G>A
  • NM_153321.3:c.449G>A
  • NM_153322.3:c.449G>A
  • NP_000295.1:p.Gly150Asp
  • NP_001268384.1:p.Gly150Asp
  • NP_001268385.1:p.Gly150Asp
  • NP_696996.1:p.Gly150Asp
  • NP_696997.1:p.Gly150Asp
  • LRG_263t1:c.449G>A
  • LRG_263:g.39377G>A
  • NC_000017.10:g.15134268C>T
  • NM_000304.2:c.449G>A
  • NM_000304.3:c.449G>A
  • NR_104017.2:n.544G>A
  • NR_104018.2:n.444G>A
  • Q01453:p.Gly150Asp
Protein change:
G150D
Links:
UniProtKB: Q01453#VAR_006379; dbSNP: rs879253954
NCBI 1000 Genomes Browser:
rs879253954
Molecular consequence:
  • NM_000304.4:c.449G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281455.2:c.449G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281456.2:c.449G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153321.3:c.449G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153322.3:c.449G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_104017.2:n.544G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_104018.2:n.444G>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
SCV000292940GeneDxcriteria provided, single submitter
Pathogenic
(Jan 4, 2017)
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, SCV000292940.10

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

Description

The G150D mutation in the PMP22 gene has been reported previously in two patients with Dejerine-Sottas neuropathy (Ionasescu et al., 1997); the patients were mother and son and the mutation had occurred de novo in the mother. The G150D mutation was not observed in approximately 6500 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 G150D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Functional studies demonstrate that the G150D mutation causes destabilization of the folded protein structure and depressed folding kinetics (Myers et al., 2008). A missense variant in the same residue (G150C) has been reported in the Human Gene Mutation Database in association with Dejerine-Sottas syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. The presence of this variant is consistent with a diagnosis of Dejerine-Sottas neuropathy

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

Last Updated: Oct 30, 2021

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