NM_000742.4(CHRNA2):c.860T>C (p.Phe287Ser) AND Autosomal dominant nocturnal frontal lobe epilepsy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 23, 2016
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:: RCV000459969.3

Allele description [Variation Report for NM_000742.4(CHRNA2):c.860T>C (p.Phe287Ser)]

NM_000742.4(CHRNA2):c.860T>C (p.Phe287Ser)

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.860T>C (p.Phe287Ser)

HGVS:

NC_000008.11:g.27463583A>G
NG_015827.1:g.20714T>C
NM_000742.4:c.860T>CMANE SELECT
NM_001282455.2:c.815T>C
NM_001347705.2:c.383T>C
NM_001347706.2:c.383T>C
NM_001347707.2:c.266T>C
NM_001347708.2:c.266T>C
NP_000733.2:p.Phe287Ser
NP_001269384.1:p.Phe272Ser
NP_001334634.1:p.Phe128Ser
NP_001334635.1:p.Phe128Ser
NP_001334636.1:p.Phe89Ser
NP_001334637.1:p.Phe89Ser
NC_000008.10:g.27321100A>G
NM_000742.3:c.860T>C

Protein change:

F128S

Links:

dbSNP: rs1060503073

NCBI 1000 Genomes Browser:

rs1060503073

Molecular consequence:

NM_000742.4:c.860T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282455.2:c.815T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001347705.2:c.383T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001347706.2:c.383T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001347707.2:c.266T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001347708.2:c.266T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000551798	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 23, 2016)	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

SCV000551798

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 23, 2016)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000551798.4

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

Description

In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CHRNA2-related disease. This sequence change replaces phenylalanine with serine at codon 287 of the CHRNA2 protein (p.Phe287Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine.

#	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: Feb 28, 2024

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