CHD2

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

Basic information

Region (hg38): 15:92886203-93027996

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
• developmental and epileptic encephalopathy 94 (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 (1827 variants)
• not_provided (620 variants)
• Inborn_genetic_diseases (194 variants)
• not_specified (142 variants)
• CHD2-related_disorder (55 variants)
• Intellectual_disability (19 variants)
• Complex_neurodevelopmental_disorder (7 variants)
• Seizure (6 variants)
• Self-limited_epilepsy_with_centrotemporal_spikes (4 variants)
• Autism_spectrum_disorder (4 variants)
• Neurodevelopmental_disorder (3 variants)
• Epilepsy (2 variants)
• See_cases (2 variants)
• Epilepsy_with_myoclonic_atonic_seizures (2 variants)
• Teratoma (1 variants)
• Secondary_microcephaly (1 variants)
• Abnormal_optic_nerve_morphology (1 variants)
• Abnormal_pinna_morphology (1 variants)
• Growth_delay (1 variants)
• Lennox-Gastaut_syndrome (1 variants)
• Microcephaly (1 variants)
• Prostate_cancer (1 variants)
• Sparse_and_thin_eyebrow (1 variants)
• Autistic_behavior (1 variants)
• History_of_neurodevelopmental_disorder (1 variants)
• CNS_hypomyelination (1 variants)
• Sparse_scalp_hair (1 variants)
• Cleft_lip/palate (1 variants)
• Neurodevelopmental_delay (1 variants)
• Hypoplasia_of_the_corpus_callosum (1 variants)
• Abnormal_facial_shape (1 variants)
• Sifrim-Hitz-Weiss_syndrome (1 variants)
• Downturned_corners_of_mouth (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. These statistics are base on transcript: NM_000001271.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		2	13	464	6	485
missense	17	74	755	132	5	983
nonsense	84	10	5			99
start loss			2			2
frameshift	112	26	11			149
splice donor/acceptor (+/-2bp)	16	27	3			46
Total	229	139	789	596	11

Highest pathogenic variant AF is 0.003239837

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