NM_015213.4(DENND5A):c.2314C>T (p.Arg772Ter) AND Developmental and epileptic encephalopathy, 49

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Dec 30, 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:: RCV000416961.2

Allele description [Variation Report for NM_015213.4(DENND5A):c.2314C>T (p.Arg772Ter)]

NM_015213.4(DENND5A):c.2314C>T (p.Arg772Ter)

Gene:

DENND5A:DENN domain containing 5A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_015213.4(DENND5A):c.2314C>T (p.Arg772Ter)

HGVS:

NC_000011.10:g.9160835G>A
NG_053019.1:g.109501C>T
NM_001243254.2:c.2314C>T
NM_001348749.2:c.2242C>T
NM_001348750.2:c.2026C>T
NM_015213.4:c.2314C>TMANE SELECT
NP_001230183.1:p.Arg772Ter
NP_001335678.1:p.Arg748Ter
NP_001335679.1:p.Arg676Ter
NP_056028.2:p.Arg772Ter
NC_000011.9:g.9182382G>A
NM_015213.3:c.2314C>T
NR_145966.2:n.2571C>T

Protein change:

R676*

Links:

dbSNP: rs1057519563

NCBI 1000 Genomes Browser:

rs1057519563

Molecular consequence:

NR_145966.2:n.2571C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001243254.2:c.2314C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001348749.2:c.2242C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001348750.2:c.2026C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_015213.4:c.2314C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 49 (DEE49)
Synonyms:: Epileptic encephalopathy, early infantile, 49
Identifiers:: MONDO: MONDO:0015002; MedGen: C4310635; OMIM: 617281

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000494580	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-HudsonAlpha	criteria provided, single submitter (HA_assertions_20161101)	Likely pathogenic (Jan 12, 2017)	unknown	research	HA_assertions_20161101.pdf, Citation Link,
SCV002819919	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Dec 30, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000494580

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

criteria provided, single submitter

(HA_assertions_20161101)

Likely pathogenic
(Jan 12, 2017)

unknown

research

HA_assertions_20161101.pdf,

Citation Link,

SCV002819919

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Dec 30, 2022)

germline

clinical testing

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
not provided	unknown	yes	1	not provided	not provided	1	not provided	research

Details of each submission

From HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-HudsonAlpha, SCV000494580.2

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

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002819919.1

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

Description

Variant summary: DENND5A c.2314C>T (p.Arg772X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2.7e-05 in 150868 control chromosomes (gnomAD v3.1.2). To our knowledge, no occurrence of c.2314C>T in individuals affected with Developmental And Epileptic Encephalopathy, 49 and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely 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: Mar 16, 2024

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