SCN2B

sodium voltage-gated channel beta subunit 2, the group of Sodium voltage-gated channel beta subunits|V-set domain containing

Basic information

Region (hg38): 11:118162805-118176639

Links

ENSG00000149575 ∙ NCBI:6327 ∙ OMIM:601327 ∙ HGNC:10589 ∙ Uniprot:O60939 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Brugada syndrome (Limited), mode of inheritance: AD
• Brugada syndrome (Supportive), mode of inheritance: AD
• familial atrial fibrillation (Supportive), mode of inheritance: AD
• atrial fibrillation, familial, 14 (Moderate), mode of inheritance: AD
• atrial fibrillation, familial, 14 (Limited), mode of inheritance: Unknown
• atrial fibrillation, familial, 14 (Limited), mode of inheritance: AD
• Brugada syndrome 1 (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Atrial fibrillation, familial 14	AD	Cardiovascular	In Atrial fibrillation, surveillance (eg, with echocardiogram and electrocardiogram) may allow early management, which may be beneficial	Cardiovascular	19808477

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCN2B gene.

• Atrial fibrillation, familial, 14 (110 variants)
• Cardiovascular phenotype (85 variants)
• not provided (29 variants)
• not specified (12 variants)
• Inborn genetic diseases (4 variants)
• Primary dilated cardiomyopathy (1 variants)
• SCN2B-related condition (1 variants)
• Variant of unknown significance (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCN2B gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				48		48
missense			82	6		88
nonsense						0
start loss						0
frameshift			3			3
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1	1		2
non coding			1	12	11	24
Total	0	0	87	66	11

Variants in SCN2B

This is a list of pathogenic ClinVar variants found in the SCN2B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-118166849-G-A			Benign (Jun 13, 2018)
11-118166882-A-C		Atrial fibrillation, familial, 14	Uncertain significance (Mar 18, 2020)
11-118166891-T-A		Cardiovascular phenotype	Uncertain significance (Dec 28, 2023)
11-118166895-C-T		Atrial fibrillation, familial, 14 • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Dec 06, 2023)
11-118166896-G-A		Atrial fibrillation, familial, 14 • Cardiovascular phenotype	Likely benign (Oct 23, 2023)
11-118166901-C-G		Cardiovascular phenotype	Uncertain significance (Dec 16, 2022)
11-118166903-T-C		Variant of unknown significance • Atrial fibrillation, familial, 14 • Cardiovascular phenotype	Uncertain significance (Aug 04, 2023)
11-118166905-C-T		Atrial fibrillation, familial, 14	Likely benign (Jul 17, 2019)
11-118166906-G-A		Atrial fibrillation, familial, 14 • Cardiovascular phenotype	Uncertain significance (Jan 08, 2024)
11-118166909-TT-GG		Atrial fibrillation, familial, 14 • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Nov 27, 2023)
11-118166913-C-T		Atrial fibrillation, familial, 14 • Cardiovascular phenotype	Uncertain significance (Jan 03, 2024)
11-118166919-C-T		Atrial fibrillation, familial, 14	Uncertain significance (Jul 19, 2022)
11-118166920-G-A		Atrial fibrillation, familial, 14 • Cardiovascular phenotype	Likely benign (Oct 07, 2021)
11-118166923-C-T		Atrial fibrillation, familial, 14 • Cardiovascular phenotype	Benign/Likely benign (Sep 04, 2023)
11-118166924-G-A		Cardiovascular phenotype • Atrial fibrillation, familial, 14	Likely benign (Sep 28, 2022)
11-118166937-C-T		Cardiovascular phenotype	Uncertain significance (Aug 31, 2021)
11-118166938-C-T		Cardiovascular phenotype	Likely benign (Jun 06, 2019)
11-118166941-G-A		Atrial fibrillation, familial, 14	Likely benign (Aug 25, 2020)
11-118166942-G-C		Cardiovascular phenotype	Uncertain significance (Dec 04, 2022)
11-118166947-C-T		Cardiovascular phenotype	Likely benign (Nov 07, 2022)
11-118166950-G-A		Atrial fibrillation, familial, 14	Likely benign (Jan 14, 2023)
11-118166957-G-A		Cardiovascular phenotype • Atrial fibrillation, familial, 14	Uncertain significance (Oct 04, 2023)
11-118166957-G-C		Atrial fibrillation, familial, 14 • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Jan 04, 2024)
11-118166959-G-A		Cardiovascular phenotype	Likely benign (Sep 13, 2020)
11-118166959-G-T		Cardiovascular phenotype	Uncertain significance (Mar 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCN2B	protein_coding	protein_coding	ENST00000278947	4	14723

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00171	0.723	125730	1	17	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.317	120	130	0.922	0.00000875	1419
Missense in Polyphen		40	51.537	0.77615		545
Synonymous	-0.765	63	55.7	1.13	0.00000400	425
Loss of Function	0.827	5	7.43	0.673	3.25e-7	93

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000870	0.0000870
Ashkenazi Jewish	0.00	0.00
East Asian	0.000598	0.000598
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000353	0.0000264
Middle Eastern	0.000598	0.000598
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-2 causes an increase in the plasma membrane surface area and in its folding into microvilli. Interacts with TNR may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier (By similarity). {ECO:0000250}.
• Disease: DISEASE: Note=Genetic variations in SCN2B may be involved in Brugada syndrome (PubMed:23559163). This tachyarrhythmia is characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269|PubMed:23559163}.
• Pathway: Antiarrhythmic Pathway, Pharmacodynamics;Developmental Biology;Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction;Interaction between L1 and Ankyrins;L1CAM interactions;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.133

Intolerance Scores

• loftool: 0.268
• rvis_EVS: -0.45
• rvis_percentile_EVS: 24

Haploinsufficiency Scores

• pHI: 0.214
• hipred: N
• hipred_score: 0.345
• ghis: 0.707

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.248

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Scn2b
• Phenotype: homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: chemical synaptic transmission;nervous system development;sodium ion transmembrane transport;response to pyrethroid;cardiac muscle contraction;regulation of atrial cardiac muscle cell membrane depolarization;cardiac muscle cell action potential involved in contraction;membrane depolarization during cardiac muscle cell action potential;regulation of heart rate by cardiac conduction;regulation of sodium ion transmembrane transporter activity
• Cellular component: voltage-gated sodium channel complex
• Molecular function: voltage-gated ion channel activity;sodium channel regulator activity;voltage-gated sodium channel activity involved in cardiac muscle cell action potential