CHD2

chromodomain helicase DNA binding protein 2, the group of DNA helicases|MicroRNA protein coding host genes

Basic information

Region (hg38): 15:92886202-93027996

Links

ENSG00000173575 ∙ NCBI:1106 ∙ OMIM:602119 ∙ HGNC:1917 ∙ Uniprot:O14647 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Lennox-Gastaut syndrome (Supportive), mode of inheritance: AD
• myoclonic-astatic epilepsy (Supportive), mode of inheritance: Unknown
• developmental and epileptic encephalopathy 94 (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Develomental and epileptic encephalopathy 94	AD	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	23020937
As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHD2 gene.

• Developmental and epileptic encephalopathy 94 (1414 variants)
• not provided (563 variants)
• Inborn genetic diseases (173 variants)
• not specified (131 variants)
• Intellectual disability (13 variants)
• CHD2-related condition (10 variants)
• Autism spectrum disorder (4 variants)
• Seizure (4 variants)
• Complex neurodevelopmental disorder (3 variants)
• Neurodevelopmental disorder (3 variants)
• CHD2-Related Disorder (2 variants)
• Childhood epilepsy with centrotemporal spikes (2 variants)
• Neurodevelopmental delay (1 variants)
• Seizure;Intellectual disability (1 variants)
• See cases (1 variants)
• Lennox-Gastaut syndrome (1 variants)
• Autistic behavior;Seizure (1 variants)
• History of neurodevelopmental disorder (1 variants)
• Developmental and epileptic encephalopathy, 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHD2 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		1	12	374	12	399
missense	9	40	544	73	6	672
nonsense	72	8	2			82
start loss						0
frameshift	86	17	5			108
inframe indel		3	12	2		17
splice donor/acceptor (+/-2bp)	8	23	1			32
splice region	3	4	43	60	4	114
non coding			4	228	112	344
Total	175	92	580	677	130

Highest pathogenic variant AF is 0.0000135

Variants in CHD2

This is a list of pathogenic ClinVar variants found in the CHD2 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-92900410-T-C		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (-)
15-92900806-G-GAC			Likely benign (Apr 10, 2018)
15-92900812-C-T		not specified	Likely benign (Apr 04, 2017)
15-92900812-C-CT		not specified	Likely benign (Feb 12, 2016)
15-92900836-A-G			Likely benign (May 03, 2018)
15-92901191-A-G		not specified	Likely benign (Apr 27, 2016)
15-92901239-T-C		Malignant tumor of prostate	Uncertain significance (-)
15-92901245-GAAAT-G		Developmental and epileptic encephalopathy 94	Pathogenic (Dec 16, 2023)
15-92901248-A-G		Developmental and epileptic encephalopathy 94 • Inborn genetic diseases	Uncertain significance (Nov 15, 2022)
15-92901249-T-G		Developmental and epileptic encephalopathy 94	Uncertain significance (Apr 21, 2021)
15-92901257-A-G		Developmental and epileptic encephalopathy 94	Uncertain significance (Aug 08, 2019)
15-92901261-C-T		Developmental and epileptic encephalopathy 94	Likely benign (Nov 13, 2023)
15-92901264-AGAG-A		Developmental and epileptic encephalopathy 94	Uncertain significance (Jul 30, 2023)
15-92901267-G-A		Developmental and epileptic encephalopathy 94	Likely benign (Nov 07, 2022)
15-92901277-T-G		Developmental and epileptic encephalopathy 94	Uncertain significance (Mar 01, 2023)
15-92901279-G-C		Developmental and epileptic encephalopathy 94	Likely benign (Sep 15, 2023)
15-92901281-T-C		Developmental and epileptic encephalopathy 94	Uncertain significance (Sep 04, 2016)
15-92901281-T-G		Developmental and epileptic encephalopathy 94	Uncertain significance (Dec 30, 2023)
15-92901282-A-G		Developmental and epileptic encephalopathy 94	Likely benign (Jul 30, 2019)
15-92901290-A-G		Developmental and epileptic encephalopathy 94	Likely benign (Apr 06, 2023)
15-92901294-A-G		Developmental and epileptic encephalopathy 94	Likely benign (Apr 29, 2020)
15-92901296-C-G		Developmental and epileptic encephalopathy 94	Uncertain significance (Jul 09, 2023)
15-92901296-C-T		Developmental and epileptic encephalopathy 94	Likely benign (Mar 10, 2021)
15-92901299-G-C			Uncertain significance (Nov 01, 2018)
15-92901302-A-G		Developmental and epileptic encephalopathy 94	Uncertain significance (Oct 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHD2	protein_coding	protein_coding	ENST00000394196	38	144712

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.37e-16	125741	0	4	125745	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.21	523	982	0.533	0.0000543	12098
Missense in Polyphen		61	273.45	0.22308		3297
Synonymous	0.714	343	360	0.952	0.0000198	3277
Loss of Function	9.50	3	111	0.0270	0.00000633	1308

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000539	0.0000462
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA-binding helicase that specifically binds to the promoter of target genes, leading to chromatin remodeling, possibly by promoting deposition of histone H3.3. Involved in myogenesis via interaction with MYOD1: binds to myogenic gene regulatory sequences and mediates incorporation of histone H3.3 prior to the onset of myogenic gene expression, promoting their expression (By similarity). {ECO:0000250}.
• Disease: DISEASE: Epileptic encephalopathy, childhood-onset (EEOC) [MIM:615369]: A severe form of epilepsy characterized by onset of multiple seizure types in the first few years of life and associated with poor prognosis. Affected individuals have cognitive regression and intellectual disability. {ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:25356899}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Prion disease pathway (Consensus)

Recessive Scores

• pRec: 0.104

Intolerance Scores

• loftool: 0.0861
• rvis_EVS: -1.75
• rvis_percentile_EVS: 2.37

Haploinsufficiency Scores

• pHI: 0.570
• hipred: Y
• hipred_score: 0.621
• ghis: 0.604

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chd2
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; limbs/digits/tail phenotype; vision/eye phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: chd2
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: increased curvature

Gene ontology

• Biological process: chromatin organization;regulation of transcription by RNA polymerase II;muscle organ development;DNA duplex unwinding
• Cellular component: nucleus;nucleoplasm;nucleolus;intracellular membrane-bounded organelle
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA binding;RNA binding;ATP-dependent DNA helicase activity;protein binding;ATP binding;histone binding