DNM2

Chr 19ADAR

dynamin 2

Also known as: CMT2M, CMTDI1, CMTDIB, DI-CMTB, DYN2, DYNII, LCCS5

DNM2 encodes dynamins that function as GTP-binding proteins involved in endocytosis and cytoskeletal interactions through self-assembly and GTPase activity. Mutations cause centronuclear myopathy 1, Charcot-Marie-Tooth disease (axonal type 2M and dominant intermediate B), and lethal congenital contracture syndrome 5 through both autosomal dominant and autosomal recessive inheritance patterns. The pathogenic mechanism involves loss of function, reflecting the protein's essential role in membrane dynamics and cellular structure.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismAD/ARLOEUF 0.184 OMIM phenotypes
VCEP Guidelines: Congenital MyopathiesReleased
ClinGen Panel
Clinical SummaryDNM2
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Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.18LOEUF
pLI 1.000
Z-score 5.66
OE 0.07 (0.030.18)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.48Z-score
OE missense 0.57 (0.520.63)
302 obs / 527.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.07 (0.030.18)
00.351.4
Missense OE0.57 (0.520.63)
00.61.4
Synonymous OE1.18
01.21.6
LoF obs/exp: 3 / 43.1Missense obs/exp: 302 / 527.0Syn Z: -2.09
DN
0.5082th %ile
GOF
0.4481th %ile
LOF
0.67top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.18
GOF1 literature citation

Literature Evidence

GOFGain-of-Function Properties of a Dynamin 2 Mutant Implicated in Charcot-Marie-Tooth DiseasePMID:34744632

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DNM2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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