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NM_000742.4(CHRNA2):c.1434C>A (p.Asp478Glu)

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(4);Likely benign(4);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
9 (Most recent: Jan 7, 2021)
Last evaluated:
Dec 4, 2020
Accession:
VCV000136753.11
Variation ID:
136753
Description:
single nucleotide variant
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NM_000742.4(CHRNA2):c.1434C>A (p.Asp478Glu)

Allele ID
140456
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
8p21.2
Genomic location
8: 27463009 (GRCh38) GRCh38 UCSC
8: 27320526 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000008.10:g.27320526G>T
NC_000008.11:g.27463009G>T
NG_015827.1:g.21288C>A
... more HGVS
Protein change
D478E, D319E, D280E, D463E
Other names
p.D478E:GAC>GAA
Canonical SPDI
NC_000008.11:27463008:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.00160 (T)

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00338
Trans-Omics for Precision Medicine (TOPMed) 0.00330
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00415
1000 Genomes Project 0.00160
The Genome Aggregation Database (gnomAD), exomes 0.00307
Links
ClinGen: CA290081
dbSNP: rs56344740
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Benign/Likely benign 2 criteria provided, multiple submitters, no conflicts Mar 13, 2017 RCV000124278.3
Benign/Likely benign 2 criteria provided, multiple submitters, no conflicts Nov 12, 2018 RCV000419685.5
Likely benign 1 criteria provided, single submitter Sep 9, 2018 RCV000717520.1
Benign 1 criteria provided, single submitter Dec 4, 2020 RCV001080927.2
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Jan 1, 2019 RCV000768183.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CHRNA2 - - GRCh38
GRCh37
473 539

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Benign
(May 13, 2013)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
GeneDx
Accession: SCV000167705.12
Submitted: (Mar 26, 2018)
Evidence details
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
Benign
(Dec 04, 2020)
criteria provided, single submitter
Method: clinical testing
Autosomal dominant nocturnal frontal lobe epilepsy
Allele origin: germline
Invitae
Accession: SCV000285613.6
Submitted: (Jan 07, 2021)
Evidence details
Likely Benign
(Sep 01, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics
Accession: SCV000511714.1
Submitted: (Feb 17, 2017)
Evidence details
Comment:
Converted during submission to Likely benign.
Likely benign
(Mar 13, 2017)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000706592.2
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Uncertain significance
(Dec 06, 2017)
criteria provided, single submitter
Method: clinical testing
Epilepsy, nocturnal frontal lobe, type 4
Allele origin: germline
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV000898604.1
Submitted: (Dec 12, 2018)
Evidence details
Comment:
CHRNA2 NM_000742.3 exon 6 p.Asp478Glu (c.1434C>A): This variant has not been reported in the literature but is present in 0.5% (685/126322) of European alleles, including … (more)
Benign
(Nov 12, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Athena Diagnostics Inc
Accession: SCV001143532.1
Submitted: (Sep 25, 2019)
Evidence details
Publications
PubMed (1)
Benign
(Jan 13, 2018)
criteria provided, single submitter
Method: clinical testing
Epilepsy, nocturnal frontal lobe, type 4
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000473182.3
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
Likely benign
(Jan 01, 2019)
criteria provided, single submitter
Method: clinical testing
Epilepsy, nocturnal frontal lobe, type 4
Allele origin: unknown
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001440254.1
Submitted: (Oct 12, 2020)
Evidence details
Likely benign
(Sep 09, 2018)
criteria provided, single submitter
Method: clinical testing
Seizures
Allele origin: germline
Ambry Genetics
Accession: SCV000848373.2
Submitted: (Nov 30, 2020)
Evidence details
Comment:
In silico models in agreement (benign);Subpopulation frequency in support of benign classification

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Two rare variations, D478N and D478E, that occur at the same amino acid residue in nicotinic acetylcholine receptor (nAChR) α2 subunit influence nAChR function. Dash B Neuropharmacology 2014 PMID: 24950454
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CHRNA2 - - - -

Text-mined citations for rs56344740...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021