NM_012062.5(DNM1L):c.1085G>A (p.Gly362Asp) AND Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jan 1, 2015
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:: RCV000239637.3

Allele description [Variation Report for NM_012062.5(DNM1L):c.1085G>A (p.Gly362Asp)]

NM_012062.5(DNM1L):c.1085G>A (p.Gly362Asp)

Gene:

DNM1L:dynamin 1 like [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p11.21

Genomic location:

Preferred name:

NM_012062.5(DNM1L):c.1085G>A (p.Gly362Asp)

HGVS:

NC_000012.12:g.32731019G>A
NG_012219.1:g.56817G>A
NM_001278463.2:c.1085G>A
NM_001278464.2:c.1124G>A
NM_001278465.2:c.1124G>A
NM_001278466.2:c.476G>A
NM_001330380.2:c.1124G>A
NM_005690.5:c.1085G>A
NM_012062.5:c.1085G>AMANE SELECT
NM_012063.4:c.1085G>A
NP_001265392.1:p.Gly362Asp
NP_001265393.1:p.Gly375Asp
NP_001265394.1:p.Gly375Asp
NP_001265395.1:p.Gly159Asp
NP_001317309.1:p.Gly375Asp
NP_005681.2:p.Gly362Asp
NP_005681.2:p.Gly362Asp
NP_036192.2:p.Gly362Asp
NP_036193.2:p.Gly362Asp
NC_000012.11:g.32883953G>A
NM_005690.4:c.1085G>A
NM_012062.4:c.1085G>A
O00429:p.Gly362Asp

Protein change:

G159D; GLY362ASP

Links:

UniProtKB: O00429#VAR_076316; OMIM: 603850.0002; dbSNP: rs879255685

NCBI 1000 Genomes Browser:

rs879255685

Molecular consequence:

NM_001278463.2:c.1085G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001278464.2:c.1124G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001278465.2:c.1124G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001278466.2:c.476G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330380.2:c.1124G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005690.5:c.1085G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_012062.5:c.1085G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_012063.4:c.1085G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1
Synonyms:: Encephalopathy due to defective mitochondrial and peroxisomal fission 1
Identifiers:: MONDO: MONDO:0013726; MedGen: C3280660; Orphanet: 330050; OMIM: 614388

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000298164	OMIM	no assertion criteria provided	Pathogenic (Oct 15, 2010)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 26604000, 20696759
SCV000965723	Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	criteria provided, single submitter (ACMG Guidelines, 2007)	Likely pathogenic (Jan 1, 2015)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000298164

OMIM

no assertion criteria provided

Pathogenic
(Oct 15, 2010)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000965723

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

criteria provided, single submitter

(ACMG Guidelines, 2007)

Likely pathogenic
(Jan 1, 2015)

de novo

clinical testing

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	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Vanstone JR, Smith AM, McBride S, Naas T, Holcik M, Antoun G, Harper ME, Michaud J, Sell E, Chakraborty P, Tetreault M; Care4Rare Consortium., Majewski J, Baird S, Boycott KM, Dyment DA, MacKenzie A, Lines MA.

Eur J Hum Genet. 2016 Jul;24(7):1084-8. doi: 10.1038/ejhg.2015.243. Epub 2015 Nov 25.

PubMed [citation]

PMID:: 26604000
PMCID:: PMC5070894

A lethal de novo mutation in the middle domain of the dynamin-related GTPase Drp1 impairs higher order assembly and mitochondrial division.

Chang CR, Manlandro CM, Arnoult D, Stadler J, Posey AE, Hill RB, Blackstone C.

J Biol Chem. 2010 Oct 15;285(42):32494-503. doi: 10.1074/jbc.M110.142430. Epub 2010 Aug 9.

PubMed [citation]

PMID:: 20696759
PMCID:: PMC2952251

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000298164.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a 7-year-old boy, born of unrelated Caucasian parents, with encephalopathy due to defective mitochondrial and peroxisomal fission-1 (EMPF1; 614388), Vanstone et al. (2016) identified a de novo heterozygous c.1085G-A transition (c.1085G-A, NM_012062.4) in exon 10 of the DNM1L gene, resulting in a gly362-to-asp (G362D) substitution in the middle domain, which is involved in homo-oligomerization. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not found in the ExAC database. The patient had severely delayed psychomotor development and onset of refractory epilepsy at about 1 year of age. Confocal microscopy of patient fibroblasts showed hyperfusion of the mitochondrial network. However, respiratory chain enzymologies in muscle and skin fibroblasts and lactate/pyruvate ratio in fibroblasts were normal, as was serum lactate. There was no evidence of peroxisomal dysfunction. Vanstone et al. (2016) noted the diagnostic difficulties given that this patient had no clinical evidence of mitochondrial dysfunction on standard screening tests, and suggested that the disorder may result from abnormal mitochondrial distribution within neurons. Functional studies of the variant were not performed, but Vanstone et al. (2016) noted that Chang et al. (2010) had demonstrated that a mutation in an adjacent residue (G363D) compromised higher-order assembly and polymerization-dependent GTPase activity, suggesting pathogenicity.

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

From Equipe Genetique des Anomalies du Developpement, Université de Bourgogne, SCV000965723.1

#	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	de novo	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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