NM_000742.4(CHRNA2):c.1259del (p.Glu420fs) AND Autosomal dominant nocturnal frontal lobe epilepsy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 18, 2024
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:: RCV003747567.2

Allele description [Variation Report for NM_000742.4(CHRNA2):c.1259del (p.Glu420fs)]

NM_000742.4(CHRNA2):c.1259del (p.Glu420fs)

Gene:

CHRNA2:cholinergic receptor nicotinic alpha 2 subunit [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

8p21.2

Genomic location:

Preferred name:

NM_000742.4(CHRNA2):c.1259del (p.Glu420fs)

HGVS:

NC_000008.11:g.27463184del
NG_015827.1:g.21113del
NG_113786.1:g.892del
NM_000742.4:c.1259delMANE SELECT
NM_001282455.2:c.1214del
NM_001347705.2:c.782del
NM_001347706.2:c.782del
NM_001347707.2:c.665del
NM_001347708.2:c.665del
NP_000733.2:p.Glu420fs
NP_001269384.1:p.Glu405fs
NP_001334634.1:p.Glu261fs
NP_001334635.1:p.Glu261fs
NP_001334636.1:p.Glu222fs
NP_001334637.1:p.Glu222fs
NC_000008.10:g.27320701del

Protein change:

E222fs

Molecular consequence:

NM_000742.4:c.1259del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282455.2:c.1214del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001347705.2:c.782del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001347706.2:c.782del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001347707.2:c.665del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001347708.2:c.665del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)
Identifiers:: MONDO: MONDO:0020300; MedGen: C3696898

Recent activity

Clear Turn Off Turn On

Taxonomy Links for GEO Profiles (Select 115363869) (1)
Taxonomy

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004559369	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 18, 2024)	germline	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

SCV004559369

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 18, 2024)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004559369.1

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

Description

This sequence change creates a premature translational stop signal (p.Glu420Glyfs*70) in the CHRNA2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 110 amino acid(s) of the CHRNA2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHRNA2-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine