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NM_001005361.3(DNM2):c.1393C>T (p.Arg465Trp) AND Charcot-Marie-Tooth disease dominant intermediate B

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Nov 17, 2023
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:
RCV000641110.10

Allele description [Variation Report for NM_001005361.3(DNM2):c.1393C>T (p.Arg465Trp)]

NM_001005361.3(DNM2):c.1393C>T (p.Arg465Trp)

Gene:
DNM2:dynamin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_001005361.3(DNM2):c.1393C>T (p.Arg465Trp)
HGVS:
  • NC_000019.10:g.10798543C>T
  • NG_008792.1:g.85465C>T
  • NM_001005360.3:c.1393C>T
  • NM_001005361.3:c.1393C>TMANE SELECT
  • NM_001005362.3:c.1393C>T
  • NM_001190716.2:c.1393C>T
  • NM_004945.4:c.1393C>T
  • NP_001005360.1:p.Arg465Trp
  • NP_001005360.1:p.Arg465Trp
  • NP_001005361.1:p.Arg465Trp
  • NP_001005362.1:p.Arg465Trp
  • NP_001177645.1:p.Arg465Trp
  • NP_004936.2:p.Arg465Trp
  • LRG_238t1:c.1393C>T
  • LRG_238:g.85465C>T
  • LRG_238p1:p.Arg465Trp
  • NC_000019.9:g.10909219C>T
  • NM_001005360.2:c.1393C>T
  • NM_001005361.3:c.1393C>T
  • P50570:p.Arg465Trp
Protein change:
R465W; ARG465TRP
Links:
UniProtKB: P50570#VAR_031965; OMIM: 602378.0006; dbSNP: rs121909091
NCBI 1000 Genomes Browser:
rs121909091
Molecular consequence:
  • NM_001005360.3:c.1393C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005361.3:c.1393C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005362.3:c.1393C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001190716.2:c.1393C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004945.4:c.1393C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Charcot-Marie-Tooth disease dominant intermediate B (CMTDIB)
Synonyms:
CHARCOT-MARIE-TOOTH NEUROPATHY, DOMINANT INTERMEDIATE B; Charcot-Marie-Tooth disease dominant intermediate 1; CMT DI1; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011674; MedGen: C1847902; Orphanet: 228179; OMIM: 606482

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000762732Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Nov 17, 2023)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV004174654Inherited Neuropathy Consortium Ii, University Of Miami
no assertion criteria provided
Uncertain significance
(Jan 6, 2016)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy.

Böhm J, Biancalana V, Dechene ET, Bitoun M, Pierson CR, Schaefer E, Karasoy H, Dempsey MA, Klein F, Dondaine N, Kretz C, Haumesser N, Poirson C, Toussaint A, Greenleaf RS, Barger MA, Mahoney LJ, Kang PB, Zanoteli E, Vissing J, Witting N, Echaniz-Laguna A, et al.

Hum Mutat. 2012 Jun;33(6):949-59. doi: 10.1002/humu.22067. Epub 2012 Apr 4.

PubMed [citation]
PMID:
22396310
PMCID:
PMC3374402

A centronuclear myopathy-dynamin 2 mutation impairs skeletal muscle structure and function in mice.

Durieux AC, Vignaud A, Prudhon B, Viou MT, Beuvin M, Vassilopoulos S, Fraysse B, Ferry A, Lainé J, Romero NB, Guicheney P, Bitoun M.

Hum Mol Genet. 2010 Dec 15;19(24):4820-36. doi: 10.1093/hmg/ddq413. Epub 2010 Sep 21.

PubMed [citation]
PMID:
20858595
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000762732.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 465 of the DNM2 protein (p.Arg465Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant centronuclear myopathy (PMID: 16227997, 22396310). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 7281). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DNM2 protein function. Experimental studies have shown that this missense change affects DNM2 function (PMID: 20858595, 22096584, 22369075, 27343996). For these reasons, this variant has been classified as Pathogenic.

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

From Inherited Neuropathy Consortium Ii, University Of Miami, SCV004174654.1

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

Last Updated: May 7, 2024