ClinVar Genomic variation as it relates to human health
NM_001005361.3(DNM2):c.1072G>A (p.Gly358Arg)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001005361.3(DNM2):c.1072G>A (p.Gly358Arg)
Variation ID: 7287 Accession: VCV000007287.12
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.2 19: 10793799 (GRCh38) [ NCBI UCSC ] 19: 10904475 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Feb 14, 2024 Mar 7, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001005361.3:c.1072G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001005361.1:p.Gly358Arg missense NM_001005360.3:c.1072G>A NP_001005360.1:p.Gly358Arg missense NM_001005362.3:c.1072G>A NP_001005362.1:p.Gly358Arg missense NM_001190716.2:c.1072G>A NP_001177645.1:p.Gly358Arg missense NM_004945.4:c.1072G>A NP_004936.2:p.Gly358Arg missense NC_000019.10:g.10793799G>A NC_000019.9:g.10904475G>A NG_008792.1:g.80721G>A LRG_238:g.80721G>A LRG_238t1:c.1072G>A LRG_238p1:p.Gly358Arg P50570:p.Gly358Arg - Protein change
- G358R
- Other names
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- Canonical SPDI
- NC_000019.10:10793798:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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DNM2 | - | - |
GRCh38 GRCh37 |
1122 | 1213 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
no assertion criteria provided
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Jul 1, 2009 | RCV000007710.4 | |
Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 7, 2023 | RCV000203266.9 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Nov 10, 2020 | RCV000369987.5 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Apr 12, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV000613145.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(Mar 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Charcot-Marie-Tooth disease dominant intermediate B
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001222989.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional … (more)
This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects DNM2 function (PMID: 22096584, 22451505, 28357347). 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. ClinVar contains an entry for this variant (Variation ID: 7287). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 18560793). It has also been observed to segregate with disease in related individuals. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 358 of the DNM2 protein (p.Gly358Arg). (less)
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Likely pathogenic
(Sep 25, 2014)
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criteria provided, single submitter
Method: research
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Charcot-Marie-Tooth disease dominant intermediate B
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
paternal
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Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine
Accession: SCV000256740.1
First in ClinVar: Jan 09, 2016 Last updated: Jan 09, 2016 |
Number of individuals with the variant: 6
Family history: yes
Sex: mixed
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Pathogenic
(Nov 10, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000329751.5
First in ClinVar: Dec 06, 2016 Last updated: Mar 08, 2017 |
Comment:
Reported in association with Charcot- Marie-Tooth disease (Gallardo et al., 2008; Yamamoto et al., 2014); Published functional studies demonstrate an impact on myelination and clathrin-mediated … (more)
Reported in association with Charcot- Marie-Tooth disease (Gallardo et al., 2008; Yamamoto et al., 2014); Published functional studies demonstrate an impact on myelination and clathrin-mediated endocytosis (Sidiropoulos et al., 2012); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 22396310, 22096584, 24065954, 19502294, 25492887, 22451505, 25259927, 18560793, 28364294) (less)
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Pathogenic
(Jul 01, 2009)
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no assertion criteria provided
Method: literature only
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CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2M
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000027911.3
First in ClinVar: Apr 04, 2013 Last updated: Aug 29, 2020 |
Comment on evidence:
In a mother and her 2 adult daughters with autosomal dominant axonal Charcot-Marie-Tooth disease type 2M (CMT2M; see 606482), Gallardo et al. (2008) identified a … (more)
In a mother and her 2 adult daughters with autosomal dominant axonal Charcot-Marie-Tooth disease type 2M (CMT2M; see 606482), Gallardo et al. (2008) identified a heterozygous 1072G-A transition in exon 7 of the DNM2 gene, resulting in a gly358-to-arg (G358R) substitution in a highly conserved region in the middle domain. The patients were ages 55, 32, and 23, and motor nerve conduction velocities were 33, 46, and 50 m/s, respectively. All had progressive gait unsteadiness and foot deformities, including pes cavus and toe clawing, in the first decade of life. All had distal muscle weakness and atrophy of the lower limbs, and the mother also had hand weakness and atrophy. Ankle reflexes were absent in all 3, and all had hypoesthesia of the lower limbs. MRI studies showed fatty infiltration of the calf muscles, particularly in the anterior compartment. The fatty infiltration increased distally and was massive in the foot musculature. Muscle edema was also present in affected muscles. In a follow-up of the family reported by Gallardo et al. (2008), Claeys et al. (2009) stated that the phenotype was consistent with axonal CMT2. (less)
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Uncertain significance
(Jan 06, 2016)
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no assertion criteria provided
Method: literature only
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Charcot-Marie-Tooth disease dominant intermediate B
Affected status: yes
Allele origin:
germline
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Inherited Neuropathy Consortium Ii, University Of Miami
Accession: SCV004174756.1
First in ClinVar: Dec 09, 2023 Last updated: Dec 09, 2023 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Insights into dynamin-associated disorders through analysis of equivalent mutations in the yeast dynamin Vps1. | Moustaq L | Microbial cell (Graz, Austria) | 2016 | PMID: 28357347 |
A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases. | Yamamoto S | Cell | 2014 | PMID: 25259927 |
Dynamin 2 mutations in Charcot-Marie-Tooth neuropathy highlight the importance of clathrin-mediated endocytosis in myelination. | Sidiropoulos PN | Brain : a journal of neurology | 2012 | PMID: 22451505 |
Mild functional differences of dynamin 2 mutations associated to centronuclear myopathy and Charcot-Marie Tooth peripheral neuropathy. | Koutsopoulos OS | PloS one | 2011 | PMID: 22096584 |
Phenotypic spectrum of dynamin 2 mutations in Charcot-Marie-Tooth neuropathy. | Claeys KG | Brain : a journal of neurology | 2009 | PMID: 19502294 |
Magnetic resonance imaging findings of leg musculature in Charcot-Marie-Tooth disease type 2 due to dynamin 2 mutation. | Gallardo E | Journal of neurology | 2008 | PMID: 18560793 |
Text-mined citations for rs267606772 ...
HelpRecord last updated May 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.