CNTN2

contactin 2, the group of Contactins|I-set domain containing

Basic information

Region (hg38): 1:205042937-205078289

Previous symbols: [ "TAX", "AXT" ]

Links

ENSG00000184144 ∙ NCBI:6900 ∙ OMIM:190197 ∙ HGNC:2172 ∙ Uniprot:Q02246 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• benign adult familial myoclonic epilepsy (Supportive), mode of inheritance: AD
• epilepsy, familial adult myoclonic, 5 (Strong), mode of inheritance: AR
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, early-onset, 5, with or without developmental delay	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	23518707

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNTN2 gene.

• Epilepsy, familial adult myoclonic, 5 (15 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNTN2 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			8	200	9	217
missense			301	13	7	321
nonsense	10					10
start loss						0
frameshift	5					5
inframe indel						0
splice donor/acceptor (+/-2bp)		9	1			10
splice region			22	34	2	58
non coding			2	95	8	105
Total	15	9	312	308	24

Highest pathogenic variant AF is 0.00000656

Variants in CNTN2

This is a list of pathogenic ClinVar variants found in the CNTN2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-205053193-C-A		Epilepsy, familial adult myoclonic, 5	Uncertain significance (Jun 04, 2022)
1-205053216-C-G		Epilepsy, familial adult myoclonic, 5	Uncertain significance (Aug 26, 2021)
1-205053224-G-A		Epilepsy, familial adult myoclonic, 5	Likely benign (Oct 13, 2023)
1-205053234-G-A		Epilepsy, familial adult myoclonic, 5	Uncertain significance (Aug 16, 2021)
1-205053236-G-A		Epilepsy, familial adult myoclonic, 5	Likely benign (Feb 23, 2020)
1-205053242-T-C		Epilepsy, familial adult myoclonic, 5	Likely benign (May 20, 2022)
1-205053247-C-T		not specified	Uncertain significance (Feb 22, 2024)
1-205053248-C-T		Epilepsy, familial adult myoclonic, 5 • CNTN2-related disorder	Benign (Jan 14, 2024)
1-205053254-A-G		Epilepsy, familial adult myoclonic, 5	Uncertain significance (Mar 26, 2022)
1-205053263-G-A		Epilepsy, familial adult myoclonic, 5	Likely benign (Jul 19, 2022)
1-205053271-T-A		Epilepsy, familial adult myoclonic, 5	Likely benign (Feb 14, 2023)
1-205057902-G-A		Epilepsy, familial adult myoclonic, 5	Likely benign (May 24, 2022)
1-205057902-G-T		Epilepsy, familial adult myoclonic, 5	Likely benign (Oct 05, 2023)
1-205057914-C-T		Epilepsy, familial adult myoclonic, 5	Likely benign (Jun 05, 2021)
1-205057915-C-A		Epilepsy, familial adult myoclonic, 5	Likely benign (Nov 01, 2022)
1-205057915-C-T		Epilepsy, familial adult myoclonic, 5	Likely benign (Mar 02, 2023)
1-205057935-C-G		Epilepsy, familial adult myoclonic, 5	Uncertain significance (Feb 24, 2022)
1-205057949-C-T		Epilepsy, familial adult myoclonic, 5	Likely benign (Oct 17, 2023)
1-205057952-C-T		Epilepsy, familial adult myoclonic, 5	Likely benign (Jun 14, 2023)
1-205057955-C-T		Epilepsy, familial adult myoclonic, 5 • CNTN2-related disorder	Benign (Jan 25, 2024)
1-205057973-C-T		Epilepsy, familial adult myoclonic, 5	Likely benign (Dec 06, 2023)
1-205057974-C-T		Epilepsy, familial adult myoclonic, 5	Pathogenic (Oct 26, 2022)
1-205057984-G-A		Epilepsy, familial adult myoclonic, 5	Uncertain significance (Jul 19, 2022)
1-205057985-T-C		Epilepsy, familial adult myoclonic, 5	Likely benign (Aug 04, 2023)
1-205057991-A-C		Epilepsy, familial adult myoclonic, 5	Likely benign (Apr 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNTN2	protein_coding	protein_coding	ENST00000331830	22	35303

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00211	0.998	125599	1	148	125748	0.000593

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.59	481	669	0.719	0.0000432	6702
Missense in Polyphen		165	269.87	0.61141		2649
Synonymous	1.02	254	276	0.922	0.0000186	2178
Loss of Function	4.92	16	55.6	0.288	0.00000324	550

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00109	0.00108
Ashkenazi Jewish	0.00179	0.00179
East Asian	0.000992	0.000979
Finnish	0.000839	0.000832
European (Non-Finnish)	0.000558	0.000545
Middle Eastern	0.000992	0.000979
South Asian	0.000131	0.000131
Other	0.000654	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: In conjunction with another transmembrane protein, CNTNAP2, contributes to the organization of axonal domains at nodes of Ranvier by maintaining voltage-gated potassium channels at the juxtaparanodal region. May be involved in cell adhesion. {ECO:0000269|PubMed:23518707}.
• Disease: DISEASE: Epilepsy, familial adult myoclonic, 5 (FAME5) [MIM:615400]: A form of cortical myoclonic tremor with epilepsy, a syndrome characterized by cortical myoclonus and variable occurrence of epileptic seizures. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom; both complex partial as well as generalized tonic clonic seizures are described. Some patients exhibit mild cognitive impairment. {ECO:0000269|PubMed:23518707}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Developmental Biology;NrCAM interactions;NCAM signaling for neurite out-growth;L1CAM interactions;NCAM1 interactions;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.188

Intolerance Scores

• loftool: 0.595
• rvis_EVS: -0.19
• rvis_percentile_EVS: 39.31

Haploinsufficiency Scores

• pHI: 0.390
• hipred: Y
• hipred_score: 0.708
• ghis: 0.510

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.402

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cntn2
• Phenotype: 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); limbs/digits/tail phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: cntn2
• Affected structure: medial longitudinal fasciculus
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: microtubule cytoskeleton organization;cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;axon guidance;axonal fasciculation;learning;adult walking behavior;positive regulation of protein processing;cerebral cortex GABAergic interneuron migration;central nervous system myelination;regulation of axon diameter;receptor internalization;clustering of voltage-gated potassium channels;negative regulation of neuron differentiation;regulation of neuronal synaptic plasticity;regulation of astrocyte differentiation;positive regulation of adenosine receptor signaling pathway;dendrite self-avoidance;protein localization to juxtaparanode region of axon;establishment of protein localization to juxtaparanode region of axon;presynaptic membrane organization
• Cellular component: plasma membrane;voltage-gated potassium channel complex;cell surface;axon;node of Ranvier;neuronal cell body;myelin sheath;juxtaparanode region of axon;synapse;anchored component of postsynaptic membrane
• Molecular function: carbohydrate binding;identical protein binding;protein self-association;cell-cell adhesion mediator activity