NM_004408.4(DNM1):c.139G>A (p.Val47Met) AND Developmental and epileptic encephalopathy, 31

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 27, 2022
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:: RCV000209889.12

Allele description [Variation Report for NM_004408.4(DNM1):c.139G>A (p.Val47Met)]

NM_004408.4(DNM1):c.139G>A (p.Val47Met)

Genes:

CIZ1:CDKN1A interacting zinc finger protein 1 [Gene - OMIM - HGNC]
DNM1:dynamin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.11

Genomic location:

Preferred name:

NM_004408.4(DNM1):c.139G>A (p.Val47Met)

HGVS:

NC_000009.12:g.128203609G>A
NG_029726.1:g.5226G>A
NG_032983.1:g.5775C>T
NM_001005336.3:c.139G>A
NM_001131015.2:c.-6+577C>T
NM_001288737.2:c.139G>A
NM_001288738.2:c.139G>A
NM_001288739.2:c.139G>A
NM_001374269.1:c.139G>A
NM_004408.4:c.139G>AMANE SELECT
NM_012127.3:c.-6+577C>T
NP_001005336.1:p.Val47Met
NP_001275666.1:p.Val47Met
NP_001275667.1:p.Val47Met
NP_001275668.1:p.Val47Met
NP_001361198.1:p.Val47Met
NP_004399.2:p.Val47Met
NC_000009.11:g.130965888G>A
NM_001288739.1:c.139G>A
NM_004408.3:c.139G>A

Protein change:

V47M

Links:

dbSNP: rs869312702

NCBI 1000 Genomes Browser:

rs869312702

Molecular consequence:

NM_001131015.2:c.-6+577C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_012127.3:c.-6+577C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001005336.3:c.139G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001288737.2:c.139G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001288738.2:c.139G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001288739.2:c.139G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374269.1:c.139G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004408.4:c.139G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 31 (DEE31A)
Synonyms:: Epileptic encephalopathy, early infantile, 31; DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 31A
Identifiers:: MONDO: MONDO:0014598; MedGen: C4225357; Orphanet: 2382; OMIM: 616346

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000265587	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-HudsonAlpha	criteria provided, single submitter (HA_assertions_20161101)	Pathogenic (Aug 7, 2015)	de novo	research	HA_assertions_20161101.pdf, Citation Link,
SCV003441462	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 27, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28554332, 34386584, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000265587

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-HudsonAlpha

criteria provided, single submitter

(HA_assertions_20161101)

Pathogenic
(Aug 7, 2015)

de novo

research

HA_assertions_20161101.pdf,

Citation Link,

SCV003441462

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 27, 2022)

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	de novo	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genomic diagnosis for children with intellectual disability and/or developmental delay.

Bowling KM, Thompson ML, Amaral MD, Finnila CR, Hiatt SM, Engel KL, Cochran JN, Brothers KB, East KM, Gray DE, Kelley WV, Lamb NE, Lose EJ, Rich CA, Simmons S, Whittle JS, Weaver BT, Nesmith AS, Myers RM, Barsh GS, Bebin EM, Cooper GM.

Genome Med. 2017 May 30;9(1):43. doi: 10.1186/s13073-017-0433-1.

PubMed [citation]

PMID:: 28554332
PMCID:: PMC5448144

Pathogenic DNM1 Gene Variant Presenting With Unusually Nonsevere Neurodevelopmental Phenotype: A Case Report.

Choi E, Dale B, RamachandranNair R, Ejaz R.

Neurol Genet. 2021 Oct;7(5):e618. doi: 10.1212/NXG.0000000000000618.

PubMed [citation]

PMID:: 34386584
PMCID:: PMC8356699

See all PubMed Citations (3)

Details of each submission

From HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-HudsonAlpha, SCV000265587.2

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

#	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

From Invitae, SCV003441462.2

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

Description

For these reasons, this variant has been classified as Pathogenic. 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) performed at Invitae indicates that this missense variant is expected to disrupt DNM1 protein function. ClinVar contains an entry for this variant (Variation ID: 224142). This missense change has been observed in individual(s) with autosomal dominant DNM1-related conditions (PMID: 28554332, 34386584). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 47 of the DNM1 protein (p.Val47Met).

#	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: Apr 20, 2024

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