NM_004408.4(DNM1):c.415G>A (p.Gly139Arg) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 2, 2018
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:: RCV002314449.9

Allele description [Variation Report for NM_004408.4(DNM1):c.415G>A (p.Gly139Arg)]

NM_004408.4(DNM1):c.415G>A (p.Gly139Arg)

Genes:

LOC113839516:Sharpr-MPRA regulatory region 8497 [Gene]
DNM1:dynamin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.11

Genomic location:

Preferred name:

NM_004408.4(DNM1):c.415G>A (p.Gly139Arg)

HGVS:

NC_000009.12:g.128219078G>A
NG_029726.1:g.20695G>A
NG_063133.1:g.429G>A
NM_001005336.3:c.415G>A
NM_001288737.2:c.415G>A
NM_001288738.2:c.415G>A
NM_001288739.2:c.415G>A
NM_004408.4:c.415G>AMANE SELECT
NP_001005336.1:p.Gly139Arg
NP_001275666.1:p.Gly139Arg
NP_001275667.1:p.Gly139Arg
NP_001275668.1:p.Gly139Arg
NP_004399.2:p.Gly139Arg
NC_000009.11:g.130981357G>A
NM_004408.2:c.415G>A

Protein change:

G139R

Links:

dbSNP: rs1564328617

NCBI 1000 Genomes Browser:

rs1564328617

Molecular consequence:

NM_001005336.3:c.415G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001288737.2:c.415G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001288738.2:c.415G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001288739.2:c.415G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004408.4:c.415G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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gi|12044012|gb|AF254046.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000848048	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Nov 2, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20428113, 28135719, 28667181 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000848048

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Nov 2, 2018)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

G domain dimerization controls dynamin's assembly-stimulated GTPase activity.

Chappie JS, Acharya S, Leonard M, Schmid SL, Dyda F.

Nature. 2010 May 27;465(7297):435-40. doi: 10.1038/nature09032. Epub 2010 Apr 28.

PubMed [citation]

PMID:: 20428113
PMCID:: PMC2879890

Prevalence and architecture of de novo mutations in developmental disorders.

Deciphering Developmental Disorders Study..

Nature. 2017 Feb 23;542(7642):433-438. doi: 10.1038/nature21062. Epub 2017 Jan 25.

PubMed [citation]

PMID:: 28135719
PMCID:: PMC6016744

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000848048.5

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

Description

The p.G139R variant (also known as c.415G>A), located in coding exon 4 of the DNM1 gene, results from a G to A substitution at nucleotide position 415. The glycine at codon 139 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been reported in the literature as de novo in an individual with epilepsy and developmental delay (McRae et al. Nature, 2017 02;542:433-438). A different variant at the same amino acid position, p.G139V, has been reported de novo in an individual with refractory seizures and profound intellectual disability (von Spiczak S et al. Neurology, 2017 Jul;89:385-394). Based on internal structural analysis, this variant is anticipated to disrupt the G3 GTP-binding motif (Ambry internal data; Chappie JS et al. Nature, 2010 May;465:435-40). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be 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

Last Updated: Oct 13, 2024

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