NM_001040142.2(SCN2A):c.605C>T (p.Ala202Val) AND multiple conditions

Clinical significance:Likely pathogenic (Last evaluated: Oct 22, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000688798.2

Allele description [Variation Report for NM_001040142.2(SCN2A):c.605C>T (p.Ala202Val)]

NM_001040142.2(SCN2A):c.605C>T (p.Ala202Val)

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.605C>T (p.Ala202Val)
HGVS:
  • NC_000002.12:g.165308794C>T
  • NG_008143.1:g.74393C>T
  • NM_001040142.2:c.605C>TMANE SELECT
  • NM_001040143.2:c.605C>T
  • NM_001371246.1:c.605C>T
  • NM_001371247.1:c.605C>T
  • NM_021007.3:c.605C>T
  • NP_001035232.1:p.Ala202Val
  • NP_001035233.1:p.Ala202Val
  • NP_001358175.1:p.Ala202Val
  • NP_001358176.1:p.Ala202Val
  • NP_066287.2:p.Ala202Val
  • NP_066287.2:p.Ala202Val
  • NC_000002.11:g.166165304C>T
  • NM_021007.2:c.605C>T
Protein change:
A202V
Links:
Molecular consequence:
  • NM_001040142.2:c.605C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001040143.2:c.605C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371246.1:c.605C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371247.1:c.605C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021007.3:c.605C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Seizures, benign familial infantile, 3 (BFIS3)
Synonyms:
CONVULSIONS, BENIGN FAMILIAL INFANTILE, 3; Convulsions benign familial neonatal; Epilepsy, benign neonatal-infantile; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011904; MedGen: C1843140; Orphanet: 140927; Orphanet: 306; OMIM: 607745
Name:
Early infantile epileptic encephalopathy 11 (DEE11)
Synonyms:
DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 11
Identifiers:
MONDO: MONDO:0013388; MedGen: C3150987; Orphanet: 1934; OMIM: 613721

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000816422Invitaecriteria provided, single submitter
Likely pathogenic
(Oct 22, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders.

Wolff M, Johannesen KM, Hedrich UBS, Masnada S, Rubboli G, Gardella E, Lesca G, Ville D, Milh M, Villard L, Afenjar A, Chantot-Bastaraud S, Mignot C, Lardennois C, Nava C, Schwarz N, GĂ©rard M, Perrin L, Doummar D, Auvin S, Miranda MJ, Hempel M, et al.

Brain. 2017 May 1;140(5):1316-1336. doi: 10.1093/brain/awx054.

PubMed [citation]
PMID:
28379373

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, SCV000816422.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces alanine with valine at codon 202 of the SCN2A protein (p.Ala202Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with benign familial neonatal seizures (PMID: 28379373). In addition, this variant has been observed to be de novo in an individual affected with neonatal epilepsy (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Nov 20, 2021

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