NM_000304.4(PMP22):c.298G>A (p.Gly100Arg) AND Dejerine-Sottas disease

Clinical significance:Pathogenic (Last evaluated: Oct 2, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000790144.2

Allele description [Variation Report for NM_000304.4(PMP22):c.298G>A (p.Gly100Arg)]

NM_000304.4(PMP22):c.298G>A (p.Gly100Arg)

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.298G>A (p.Gly100Arg)
HGVS:
  • NC_000017.11:g.15239492C>T
  • NG_007949.1:g.30836G>A
  • NM_000304.4:c.298G>AMANE SELECT
  • NM_001281455.2:c.298G>A
  • NM_001281456.2:c.298G>A
  • NM_001330143.2:c.298G>A
  • NM_153321.3:c.298G>A
  • NM_153322.3:c.298G>A
  • NP_000295.1:p.Gly100Arg
  • NP_001268384.1:p.Gly100Arg
  • NP_001268385.1:p.Gly100Arg
  • NP_001317072.1:p.Gly100Arg
  • NP_696996.1:p.Gly100Arg
  • NP_696997.1:p.Gly100Arg
  • LRG_263:g.30836G>A
  • NC_000017.10:g.15142809C>T
  • NM_000304.3:c.298G>A
  • NM_153322.2:c.298G>A
  • NR_104017.2:n.393G>A
  • NR_104018.2:n.293G>A
Protein change:
G100R
Links:
dbSNP: rs1597607651
NCBI 1000 Genomes Browser:
rs1597607651
Molecular consequence:
  • NM_000304.4:c.298G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281455.2:c.298G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281456.2:c.298G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330143.2:c.298G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153321.3:c.298G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153322.3:c.298G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_104017.2:n.393G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_104018.2:n.293G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Name:
Dejerine-Sottas disease
Synonyms:
CHARCOT-MARIE-TOOTH DISEASE, TYPE 3; HEREDITARY MOTOR AND SENSORY NEUROPATHY TYPE III; HMSN Type III; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007790; MedGen: C0011195; Orphanet: 64748; OMIM: 145900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000929535Inherited Neuropathy Consortiumno assertion criteria providedUncertain significancegermlineliterature only

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

SCV0020123463billioncriteria provided, single submitter
Pathogenic
(Oct 2, 2021)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedliterature only, clinical testing

Citations

PubMed

Mutational analysis of the MPZ, PMP22 and Cx32 genes in patients of Spanish ancestry with Charcot-Marie-Tooth disease and hereditary neuropathy with liability to pressure palsies.

Bort S, Nelis E, Timmerman V, Sevilla T, Cruz-Martínez A, Martínez F, Millán JM, Arpa J, Vílchez JJ, Prieto F, Van Broeckhoven C, Palau F.

Hum Genet. 1997 Jun;99(6):746-54.

PubMed [citation]
PMID:
9187667

Dejerine-Sottas neuropathy and PMP22 point mutations: a new base pair substitution and a possible "hot spot" on Ser72.

Marques W Jr, Thomas PK, Sweeney MG, Carr L, Wood NW.

Ann Neurol. 1998 May;43(5):680-3.

PubMed [citation]
PMID:
9585367
See all PubMed Citations (3)

Details of each submission

From Inherited Neuropathy Consortium, SCV000929535.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From 3billion, SCV002012346.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The missense variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PM1). It is not observed in the gnomAD v2.1.1 dataset (PM2). A different missense change at the same codon (p.Gly100Gln) has been reported as pathogenic/likely pathogenic with strong evidence (PMID:9585367, PM5). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.956, 3Cnet: 0.994, PP3). Patient's phenotype is considered compatible with Hypertrophic Neuropathy of Dejerine-Sottas (3billion dataset, PP4). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Nov 27, 2021

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