NM_001005361.3(DNM2):c.869G>A (p.Arg290Gln) AND Charcot-Marie-Tooth disease dominant intermediate B

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 8, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001007469.7

Allele description [Variation Report for NM_001005361.3(DNM2):c.869G>A (p.Arg290Gln)]

NM_001005361.3(DNM2):c.869G>A (p.Arg290Gln)

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.869G>A (p.Arg290Gln)

HGVS:

NC_000019.10:g.10786583G>A
NG_008792.1:g.73505G>A
NM_001005360.3:c.869G>A
NM_001005361.3:c.869G>AMANE SELECT
NM_001005362.3:c.869G>A
NM_001190716.2:c.869G>A
NM_004945.4:c.869G>A
NP_001005360.1:p.Arg290Gln
NP_001005360.1:p.Arg290Gln
NP_001005361.1:p.Arg290Gln
NP_001005362.1:p.Arg290Gln
NP_001177645.1:p.Arg290Gln
NP_004936.2:p.Arg290Gln
LRG_238t1:c.869G>A
LRG_238:g.73505G>A
LRG_238p1:p.Arg290Gln
NC_000019.9:g.10897259G>A
NM_001005360.2:c.869G>A

Protein change:

R290Q

Links:

dbSNP: rs117398902

NCBI 1000 Genomes Browser:

rs117398902

Molecular consequence:

NM_001005360.3:c.869G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001005361.3:c.869G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001005362.3:c.869G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001190716.2:c.869G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004945.4:c.869G>A - 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
SCV001167084	Kariminejad - Najmabadi Pathology & Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001230660	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 8, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 32657593, 33333461, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001167084

Kariminejad - Najmabadi Pathology & Genetics Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

germline

clinical testing

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

SCV001230660

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 8, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Molecular Diagnosis of Hereditary Neuropathies by Whole Exome Sequencing and Expanding the Phenotype Spectrum.

Taghizadeh S, Vazehan R, Beheshtian M, Sadeghinia F, Fattahi Z, Mohseni M, Arzhangi S, Nafissi S, Kariminejad A, Najmabadi H, Kahrizi K.

Arch Iran Med. 2020 Jul 1;23(7):426-433. doi: 10.34172/aim.2020.39.

PubMed [citation]

PMID:: 32657593

See all PubMed Citations (4)

Details of each submission

From Kariminejad - Najmabadi Pathology & Genetics Center, SCV001167084.1

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001230660.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 290 of the DNM2 protein (p.Arg290Gln). This variant is present in population databases (rs117398902, gnomAD 0.006%). This missense change has been observed in individuals with Charcot-Marie-Tooth disease and/or congenital myopathy (PMID: 32657593, 33333461). ClinVar contains an entry for this variant (Variation ID: 816534). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

Last Updated: Sep 29, 2024

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