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:: RCV000641110.11

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)

Other names:

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

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000762732	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 17, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 16227997, 22396310, 20858595, 22096584, 22369075, 27343996, 28492532
SCV004174654	Inherited Neuropathy Consortium Ii, University Of Miami	no assertion criteria provided	Uncertain significance (Jan 6, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000762732

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 17, 2023)

germline

clinical testing

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

SCV004174654

Inherited Neuropathy Consortium Ii, University Of Miami

no assertion criteria provided

Uncertain significance
(Jan 6, 2016)

germline

literature only

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000762732.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	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

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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