NM_000748.3(CHRNB2):c.953T>C (p.Val318Ala) AND Autosomal dominant nocturnal frontal lobe epilepsy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 4, 2022
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:: RCV002038254.6

Allele description [Variation Report for NM_000748.3(CHRNB2):c.953T>C (p.Val318Ala)]

NM_000748.3(CHRNB2):c.953T>C (p.Val318Ala)

Gene:

CHRNB2:cholinergic receptor nicotinic beta 2 subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q21.3

Genomic location:

Preferred name:

NM_000748.3(CHRNB2):c.953T>C (p.Val318Ala)

HGVS:

NC_000001.11:g.154571776T>C
NG_008027.1:g.8996T>C
NM_000748.3:c.953T>CMANE SELECT
NP_000739.1:p.Val318Ala
NC_000001.10:g.154544252T>C

Protein change:

V318A

Links:

dbSNP: rs2101521543

NCBI 1000 Genomes Browser:

rs2101521543

Molecular consequence:

NM_000748.3:c.953T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Homo sapiens zinc finger protein 428, mRNA (cDNA clone MGC:51082 IMAGE:4813427),...
Homo sapiens zinc finger protein 428, mRNA (cDNA clone MGC:51082 IMAGE:4813427), complete cds
gi|28279078|gb|BC045799.1|

Nucleotide
Human chromosome 14 DNA sequence BAC R-649E7 of library RPCI-11 from chromosome ...
Human chromosome 14 DNA sequence BAC R-649E7 of library RPCI-11 from chromosome 14 of Homo sapiens (Human), complete sequence
gi|15424523|emb|AL139099.3|

Nucleotide
sulfate ABC transporter, sulfate-binding family protein [Burkholderia multivoran...
sulfate ABC transporter, sulfate-binding family protein [Burkholderia multivorans]
gi|685690426|gnl|LANL|DM80_39|gb|AI 2.1|

Protein
barstar family protein [Burkholderia multivorans]
barstar family protein [Burkholderia multivorans]
gi|685690429|gnl|LANL|DM80_1037|gb| 545.1|

Protein

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
SCV002294485	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 4, 2022)	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

SCV002294485

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 4, 2022)

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, SCV002294485.3

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

Description

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. 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 CHRNB2 protein function. This missense change has been observed in individual(s) with clinical features of autosomal dominant nocturnal frontal lobe epilepsy (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 318 of the CHRNB2 protein (p.Val318Ala).

#	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