Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

SCN2A

HGNC:10588 (protein-coding gene)

sodium voltage-gated channel alpha subunit 2

Unique Cases:
125
Disorders:
ID, ASD, EP, ADHD, SCZ, CP
Last Updated:
January 24, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
SCN2A is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.
Gene Function
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:1325650, PubMed:17021166, PubMed:28256214, PubMed:29844171). Implicated in the regulation of hippocampal replay occurring within sharp wave ripples (SPW-R) important for memory (By simi... (Source: Uniprot)
Previous symbols
SCN2A1, SCN2A2
Alias symbols
Nav1.2, HBSCII, HBSCI
Chromosomal Location
2q24.3
Genomic Coordinates
GRCh37:chr2:166095912-166248820
GRCh38:chr2:165208056-165392310
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

4.08

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.13

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

Definitive

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Definitive3 Strong4 Supportive6

Publications:

De Rubeis S et. al., Synaptic, transcriptional and chromatin genes disrupted in autism., Nature, 2014
Yang L et. al., Clinical and genetic spectrum of a large cohort of children with epilepsy in China., Genet Med, 2019
Guo H et. al., Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model., Mol Autism, 2018
Wang T et. al., De novo genic mutations among a Chinese autism spectrum disorder cohort., Nat Commun, 2016
Kothur K et. al., Diagnostic yield of targeted massively parallel sequencing in children with epileptic encephalopathy., Seizure, 2018
D'Gama AM et. al., Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms., Neuron, 2015
Yuen RK et. al., Whole-genome sequencing of quartet families with autism spectrum disorder., Nat Med, 2015
Deciphering Developmental Disorders Study. et. al., Large-scale discovery of novel genetic causes of developmental disorders., Nature, 2015
Trujillano D et. al., Clinical exome sequencing: results from 2819 samples reflecting 1000 families., Eur J Hum Genet, 2017
Yamamoto T et. al., Genomic backgrounds of Japanese patients with undiagnosed neurodevelopmental disorders., Brain Dev, 2019
Diets IJ et. al., High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer., Clin Cancer Res, 2018
Horvath GA et. al., Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target?, Mol Genet Metab, 2016
Jiang T et. al., Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy., Front Mol Neurosci, 2021
Coe BP et. al., Refining analyses of copy number variation identifies specific genes associated with developmental delay., Nat Genet, 2014
et. al., , ,
Beighley JS et. al., Clinical Phenotypes of Carriers of Mutations in CHD8 or Its Conserved Target Genes., Biol Psychiatry, 2020
Carvill GL et. al., Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1., Nat Genet, 2013
Gilissen C et. al., Genome sequencing identifies major causes of severe intellectual disability., Nature, 2014
Grozeva D et. al., Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability., Hum Mutat, 2015
Trump N et. al., Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis., J Med Genet, 2016
Tran KT et. al., Genetic landscape of autism spectrum disorder in Vietnamese children., Sci Rep, 2020
Al Zahrani H et. al., Genomics in Cerebral Palsy phenotype across the lifespan: Comparison of diagnostic yield between children and adult population., Mol Genet Metab, 2021
Rees E et. al., De novo mutations identified by exome sequencing implicate rare missense variants in SLC6A1 in schizophrenia., Nat Neurosci, 2020
Sun D et. al., Detection of Disease-Causing SNVs/Indels and CNVs in Single Test Based on Whole Exome Sequencing: A Retrospective Case Study in Epileptic Encephalopathies., Front Pediatr, 2021
Miyake N et. al., Molecular diagnosis of 405 individuals with autism spectrum disorder., Eur J Hum Genet, 2023
Tavassoli T et. al., De novo SCN2A splice site mutation in a boy with Autism spectrum disorder., BMC Med Genet, 2014
Lee HH et. al., Successful Adaptation of Targeted Gene Panel Next-Generation Sequencing in Regional Hospital in Hong Kong: Genomic Diagnosis of SCN2A-Related Seizure Disorder., Chin Med J (Engl), 2018
Kamiya K et. al., A nonsense mutation of the sodium channel gene SCN2A in a patient with intractable epilepsy and mental decline., J Neurosci, 2004
Franciosi S et. al., De novo nonsense mutations in the sodium channel gene, SCN2A, in sporadic intractable epilepsy., Clin Genet, 2010
Carroll LS et. al., Mutation screening of SCN2A in schizophrenia and identification of a novel loss-of-function mutation., Psychiatr Genet, 2016
Kurul SH et. al., High diagnostic rate of trio exome sequencing in consanguineous families with neurogenetic diseases., Brain, 2021
Salinas V et. al., Clinical next generation sequencing in developmental and epileptic encephalopathies: Diagnostic relevance of data re-analysis and variants re-interpretation., Eur J Med Genet, 2021

NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.
Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.
DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.
SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.
ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.
GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
gnomAD
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