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NM_001040142.2(SCN2A):c.5704C>T (p.Arg1902Cys) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 25, 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:
RCV003458640.1

Allele description [Variation Report for NM_001040142.2(SCN2A):c.5704C>T (p.Arg1902Cys)]

NM_001040142.2(SCN2A):c.5704C>T (p.Arg1902Cys)

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.5704C>T (p.Arg1902Cys)
Other names:
p.Arg1902Cys
HGVS:
  • NC_000002.12:g.165389510C>T
  • NG_008143.1:g.155109C>T
  • NM_001040142.2:c.5704C>TMANE SELECT
  • NM_001040143.2:c.5704C>T
  • NM_001371246.1:c.5704C>T
  • NM_001371247.1:c.5704C>T
  • NM_021007.3:c.5704C>T
  • NP_001035232.1:p.Arg1902Cys
  • NP_001035233.1:p.Arg1902Cys
  • NP_001358175.1:p.Arg1902Cys
  • NP_001358176.1:p.Arg1902Cys
  • NP_066287.2:p.Arg1902Cys
  • NC_000002.11:g.166246020C>T
  • NM_021007.2:c.5704C>T
  • NM_021007.3:c.5704C>T
Protein change:
R1902C
Links:
dbSNP: rs367833365
NCBI 1000 Genomes Browser:
rs367833365
Molecular consequence:
  • NM_001040142.2:c.5704C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001040143.2:c.5704C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371246.1:c.5704C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371247.1:c.5704C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021007.3:c.5704C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Autism (AUTS)
Synonyms:
Autistic disorder; Autistic disorder of childhood onset
Identifiers:
MONDO: MONDO:0005260; MeSH: D001321; MedGen: C0004352; OMIM: 209850; Human Phenotype Ontology: HP:0000717
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:
Episodic ataxia, type 9
Identifiers:
MONDO: MONDO:0030064; MedGen: C5394520; OMIM: 618924
Name:
Developmental and epileptic encephalopathy, 76
Synonyms:
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 76; DEVELOPMENTAL DELAY, EPILEPTIC ENCEPHALOPATHY, CEREBRAL ATROPHY, AND ABNORMAL MYELINATION
Identifiers:
MONDO: MONDO:0032768; MedGen: C5193113; OMIM: 618468

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004177209Clinical Genomics Laboratory, Washington University in St. Louis
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Aug 25, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Clinical Genomics Laboratory, Washington University in St. Louis, SCV004177209.1

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

Description

The SCN2A c.5704C>T (p.Arg1902Cys) variant has been reported in two unrelated individuals affected with autism (Stessman HA et al., PMID: 28191899; Weiss LA et al., PMID: 12610651) but was not detected in the affected sibling reported by Weiss and colleagues (PMID: 12610651). Functional evidence shows a Ca2+ dependent conformational change in Nav1.2 C-terminus-CaM complex and a reduced affinity for the low-affinity binding site for calcium-bound calmodulin, indicating that this variant impacts protein function (Kim J et al., PMID: 15316014; Weiss LA et al., PMID: 12610651). The variant is only observed on 8 alleles of 282,094 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors indicate that the variant is damaging, evidence that correlates with impact to SCN2A function. This variant has been reported in the ClinVar database as a variant of uncertain significance by two submitters. Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.

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

Last Updated: Nov 24, 2024