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NM_001040142.2(SCN2A):c.787G>A (p.Ala263Thr) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 11, 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:
RCV001382401.7

Allele description [Variation Report for NM_001040142.2(SCN2A):c.787G>A (p.Ala263Thr)]

NM_001040142.2(SCN2A):c.787G>A (p.Ala263Thr)

Gene:
SCN2A:sodium voltage-gated channel alpha subunit 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q24.3
Genomic location:
Preferred name:
NM_001040142.2(SCN2A):c.787G>A (p.Ala263Thr)
HGVS:
  • NC_000002.12:g.165310412G>A
  • NG_008143.1:g.76011G>A
  • NM_001040142.2:c.787G>AMANE SELECT
  • NM_001040143.2:c.787G>A
  • NM_001371246.1:c.787G>A
  • NM_001371247.1:c.787G>A
  • NM_021007.3:c.787G>A
  • NP_001035232.1:p.Ala263Thr
  • NP_001035233.1:p.Ala263Thr
  • NP_001358175.1:p.Ala263Thr
  • NP_001358176.1:p.Ala263Thr
  • NP_066287.2:p.Ala263Thr
  • NC_000002.11:g.166166922G>A
  • NM_021007.2:c.787G>A
Protein change:
A263T
Links:
dbSNP: rs1697364931
NCBI 1000 Genomes Browser:
rs1697364931
Molecular consequence:
  • NM_001040142.2:c.787G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001040143.2:c.787G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371246.1:c.787G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371247.1:c.787G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021007.3:c.787G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
  • Increase in persistent current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0040]
  • Overall gain-of-function [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0137]

Condition(s)

Name:
Seizures, benign familial infantile, 3 (BFIS3)
Synonyms:
CONVULSIONS, BENIGN FAMILIAL INFANTILE, 3; Familial neonatal seizures
Identifiers:
MONDO: MONDO:0011904; MedGen: C1843140; Orphanet: 140927; Orphanet: 306; OMIM: 607745
Name:
Developmental and epileptic encephalopathy, 11 (DEE11)
Synonyms:
Early infantile epileptic encephalopathy 11
Identifiers:
MONDO: MONDO:0013388; MedGen: C3150987; Orphanet: 1934; OMIM: 613721

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001581153Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 11, 2022) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain.

Liao Y, Anttonen AK, Liukkonen E, Gaily E, Maljevic S, Schubert S, Bellan-Koch A, Petrou S, Ahonen VE, Lerche H, Lehesjoki AE.

Neurology. 2010 Oct 19;75(16):1454-8. doi: 10.1212/WNL.0b013e3181f8812e.

PubMed [citation]
PMID:
20956790

Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia.

Schwarz N, Hahn A, Bast T, Müller S, Löffler H, Maljevic S, Gaily E, Prehl I, Biskup S, Joensuu T, Lehesjoki AE, Neubauer BA, Lerche H, Hedrich UBS.

J Neurol. 2016 Feb;263(2):334-343. doi: 10.1007/s00415-015-7984-0. Epub 2015 Dec 8.

PubMed [citation]
PMID:
26645390
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001581153.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ala263 amino acid residue in SCN2A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20956790, 26645390, 27159988, 28065826). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1070304). This missense change has been observed in individual(s) with early-onset epileptic encephalopathies (PMID: 23935176). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 263 of the SCN2A protein (p.Ala263Thr).

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

Last Updated: Sep 29, 2024