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NM_001040142.2(SCN2A):c.635A>G (p.Asn212Ser) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 23, 2023
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:
RCV001943689.4

Allele description [Variation Report for NM_001040142.2(SCN2A):c.635A>G (p.Asn212Ser)]

NM_001040142.2(SCN2A):c.635A>G (p.Asn212Ser)

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.635A>G (p.Asn212Ser)
HGVS:
  • NC_000002.12:g.165309381A>G
  • NG_008143.1:g.74980A>G
  • NM_001040142.2:c.635A>GMANE SELECT
  • NM_001040143.2:c.697+125A>G
  • NM_001371246.1:c.697+125A>G
  • NM_001371247.1:c.635A>G
  • NM_021007.3:c.635A>G
  • NP_001035232.1:p.Asn212Ser
  • NP_001358176.1:p.Asn212Ser
  • NP_066287.2:p.Asn212Ser
  • NC_000002.11:g.166165891A>G
Protein change:
N212S
Links:
dbSNP: rs2105244912
NCBI 1000 Genomes Browser:
rs2105244912
Molecular consequence:
  • NM_001040143.2:c.697+125A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001371246.1:c.697+125A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001040142.2:c.635A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371247.1:c.635A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021007.3:c.635A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002194909Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Mar 23, 2023) 		germlineclinical testing

PubMed (2)
[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

Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome.

Nakamura K, Kato M, Osaka H, Yamashita S, Nakagawa E, Haginoya K, Tohyama J, Okuda M, Wada T, Shimakawa S, Imai K, Takeshita S, Ishiwata H, Lev D, Lerman-Sagie T, Cervantes-Barragán DE, Villarroel CE, Ohfu M, Writzl K, Gnidovec Strazisar B, Hirabayashi S, Chitayat D, et al.

Neurology. 2013 Sep 10;81(11):992-8. doi: 10.1212/WNL.0b013e3182a43e57. Epub 2013 Aug 9.

PubMed [citation]
PMID:
23935176

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, SCV002194909.3

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

Description

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. This variant disrupts the p.Asn212 amino acid residue in SCN2A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23935176). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 SCN2A protein function. ClinVar contains an entry for this variant (Variation ID: 1420984). This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 212 of the SCN2A protein (p.Asn212Ser).

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

Last Updated: Sep 29, 2024