NM_000742.4(CHRNA2):c.1434C>A (p.Asp478Glu) AND Epilepsy, nocturnal frontal lobe, type 4

Clinical significance:Conflicting interpretations of pathogenicity, Benign(1);Likely benign(1);Uncertain significance(1) (Last evaluated: Jan 1, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000768183.3

Allele description [Variation Report for NM_000742.4(CHRNA2):c.1434C>A (p.Asp478Glu)]

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

Gene:
CHRNA2:cholinergic receptor nicotinic alpha 2 subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8p21.2
Genomic location:
Preferred name:
NM_000742.4(CHRNA2):c.1434C>A (p.Asp478Glu)
Other names:
p.D478E:GAC>GAA
HGVS:
  • NC_000008.11:g.27463009G>T
  • NG_015827.1:g.21288C>A
  • NM_000742.4:c.1434C>AMANE SELECT
  • NM_001282455.2:c.1389C>A
  • NM_001347705.2:c.957C>A
  • NM_001347706.2:c.957C>A
  • NM_001347707.2:c.840C>A
  • NM_001347708.2:c.840C>A
  • NP_000733.2:p.Asp478Glu
  • NP_001269384.1:p.Asp463Glu
  • NP_001334634.1:p.Asp319Glu
  • NP_001334635.1:p.Asp319Glu
  • NP_001334636.1:p.Asp280Glu
  • NP_001334637.1:p.Asp280Glu
  • NC_000008.10:g.27320526G>T
  • NM_000742.3:c.1434C>A
Protein change:
D280E
Links:
dbSNP: rs56344740
NCBI 1000 Genomes Browser:
rs56344740
Molecular consequence:
  • NM_000742.4:c.1434C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282455.2:c.1389C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001347705.2:c.957C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001347706.2:c.957C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001347707.2:c.840C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001347708.2:c.840C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Epilepsy, nocturnal frontal lobe, type 4 (ENFL4)
Synonyms:
EPILEPSY, FAMILIAL, WITH NOCTURNAL WANDERING AND ICTAL FEAR; Autosomal dominant nocturnal frontal lobe epilepsy type 4
Identifiers:
MONDO: MONDO:0012474; MedGen: C1835905; Orphanet: 98784; OMIM: 610353

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000473182Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Benign
(Jan 13, 2018)
germlineclinical testing

Citation Link,

SCV000898604Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicagocriteria provided, single submitter
Uncertain significance
(Dec 6, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001440254Institute of Human Genetics, University of Leipzig Medical Centercriteria provided, single submitter
Likely benign
(Jan 1, 2019)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000473182.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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 by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV000898604.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

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 1 homozygote, in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs56344740). This variant is present in ClinVar, with several labs classifying this variant as likely benign or benign (Variation ID:136753). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. Functional studies predict that this variant will impact the protein (Dash 2014 PMID:24950454). However, these studies may not accurately represent human biological function. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001440254.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2021

Support Center