SMARCA2

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2, the group of Bromodomain containing|BAF complex|GBAF complex

Basic information

Region (hg38): 9:1980289-2193624

Previous symbols: [ "SNF2L2" ]

Links

ENSG00000080503 ∙ NCBI:6595 ∙ OMIM:600014 ∙ HGNC:11098 ∙ Uniprot:P51531 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Coffin-Siris syndrome 1 (Definitive), mode of inheritance: AD
• intellectual disability-sparse hair-brachydactyly syndrome (Definitive), mode of inheritance: AD
• intellectual disability-sparse hair-brachydactyly syndrome (Supportive), mode of inheritance: AD
• intellectual disability-sparse hair-brachydactyly syndrome (Definitive), mode of inheritance: AD
• intellectual disability-sparse hair-brachydactyly syndrome (Strong), mode of inheritance: AD
• intellectual disability-sparse hair-brachydactyly syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Blepharophimosis-impaired intellectual development syndrome	AD	Allergy/Immunology/Infectious	Among other features, the condition can involve recurrent respiratory infections, and awareness may allow preventative measures and early and aggressive treatment of infections	Allergy/Immunology/Infectious; Craniofacial; Dental; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic	19606471; 22366787; 22822383; 25249037; 32694869

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMARCA2 gene.

• not provided (741 variants)
• Nicolaides-Baraitser syndrome (205 variants)
• Inborn genetic diseases (162 variants)
• not specified (43 variants)
• Blepharophimosis-impaired intellectual development syndrome (17 variants)
• Intellectual disability (13 variants)
• SMARCA2-related BAFopathy (9 variants)
• SMARCA2-related condition (7 variants)
• Nicolaides-Baraitser syndrome;Blepharophimosis-impaired intellectual development syndrome (7 variants)
• Blepharophimosis-impaired intellectual development syndrome;Nicolaides-Baraitser syndrome (3 variants)
• Coffin Siris/Intellectual Disability (2 variants)
• - (2 variants)
• Neurodevelopmental delay (2 variants)
• Autism spectrum disorder (2 variants)
• Nicolaides-Baraitser syndrome;Coffin-Siris syndrome 1 (1 variants)
• Blepharophimosis;Intellectual disability (1 variants)
• Developmental disorder (1 variants)
• Neurodevelopmental disorder (1 variants)
• Hirsutism;Intellectual disability (1 variants)
• See cases (1 variants)
• Pituitary stalk interruption syndrome (1 variants)
• Nicolaides-Baraitser syndrome;Coffin-Siris syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMARCA2 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			16	133	24	173
missense	30	47	197	59	12	345
nonsense			7			7
start loss						0
frameshift		1	6			7
inframe indel		1	18	22	2	43
splice donor/acceptor (+/-2bp)		1	3	1		5
splice region			11	20	4	35
non coding			26	119	155	300
Total	30	50	273	334	193

Highest pathogenic variant AF is 0.00000657

Variants in SMARCA2

This is a list of pathogenic ClinVar variants found in the SMARCA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-2015385-G-A		Nicolaides-Baraitser syndrome	Uncertain significance (Mar 30, 2018)
9-2015405-G-T		Nicolaides-Baraitser syndrome • Blepharophimosis-impaired intellectual development syndrome	Uncertain significance (Aug 20, 2023)
9-2028757-T-G			Benign (Aug 08, 2018)
9-2028782-T-C			Likely benign (Aug 17, 2018)
9-2028942-A-G			Benign (Aug 08, 2018)
9-2029018-G-A		not specified • Nicolaides-Baraitser syndrome • Inborn genetic diseases	Benign (Jul 03, 2018)
9-2029030-C-T		Inborn genetic diseases	Likely benign (Aug 02, 2021)
9-2029031-G-A			Likely benign (Apr 14, 2023)
9-2029049-G-A			Likely benign (May 15, 2023)
9-2029053-C-A		Nicolaides-Baraitser syndrome	Uncertain significance (Dec 18, 2017)
9-2029053-C-T			Benign (Aug 03, 2023)
9-2029072-C-T		Inborn genetic diseases	Likely benign (Feb 27, 2024)
9-2029073-G-A			Likely benign (Jan 24, 2024)
9-2029073-G-C		Inborn genetic diseases	Benign/Likely benign (May 02, 2023)
9-2029075-G-A			Uncertain significance (Oct 20, 2023)
9-2029089-C-T		Autism spectrum disorder	Likely benign (Apr 13, 2022)
9-2029099-T-C			Uncertain significance (Dec 16, 2023)
9-2029119-C-T		Nicolaides-Baraitser syndrome • Inborn genetic diseases • SMARCA2-related disorder	Benign/Likely benign (Nov 01, 2023)
9-2029126-C-T			Likely benign (Aug 17, 2023)
9-2029127-A-G		Nicolaides-Baraitser syndrome	Uncertain significance (Jan 13, 2018)
9-2029135-G-A			Uncertain significance (Nov 22, 2023)
9-2029139-C-T		Inborn genetic diseases	Likely benign (Nov 29, 2017)
9-2029140-G-A		Inborn genetic diseases	Likely benign (Nov 17, 2022)
9-2029152-A-G			Uncertain significance (Nov 15, 2023)
9-2029156-G-C			Likely benign (Dec 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMARCA2	protein_coding	protein_coding	ENST00000382203	33	178283

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.77e-7	125579	1	168	125748	0.000672

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.05	476	904	0.527	0.0000535	10486
Missense in Polyphen		69	109.77	0.62859		1228
Synonymous	-4.19	430	333	1.29	0.0000202	2955
Loss of Function	7.69	11	89.6	0.123	0.00000493	1020

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000520	0.000428
Ashkenazi Jewish	0.00	0.00
East Asian	0.000170	0.000163
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000232	0.000202
Middle Eastern	0.000170	0.000163
South Asian	0.00817	0.00432
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically (PubMed:22952240, PubMed:26601204). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250|UniProtKB:Q6DIC0, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}.
• Disease: DISEASE: Nicolaides-Baraitser syndrome (NCBRS) [MIM:601358]: A rare disorder characterized by severe mental retardation with absent or limited speech, seizures, short stature, sparse hair, typical facial characteristics, brachydactyly, prominent finger joints and broad distal phalanges. Some of the features are progressive with time. {ECO:0000269|PubMed:22366787, ECO:0000269|PubMed:22426308, ECO:0000269|PubMed:23906836, ECO:0000269|PubMed:27665729}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Schizophrenia (SCZD) [MIM:181500]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. {ECO:0000269|PubMed:19363039}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.
• Pathway: Thermogenesis - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Retinoblastoma (RB) in Cancer;Pathways Affected in Adenoid Cystic Carcinoma;VEGFA-VEGFR2 Signaling Pathway;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;Generic Transcription Pathway;RNA Polymerase II Transcription;RMTs methylate histone arginines;Chromatin modifying enzymes;Chromatin organization;C-MYB transcription factor network;Transcriptional regulation by RUNX1;Regulation of Androgen receptor activity;E2F transcription factor network (Consensus)

Recessive Scores

• pRec: 0.516

Intolerance Scores

• loftool: 0.0940
• rvis_EVS: -1.97
• rvis_percentile_EVS: 1.82

Haploinsufficiency Scores

• pHI: 1.00
• hipred: Y
• hipred_score: 0.704
• ghis: 0.662

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.931

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smarca2
• Phenotype: digestive/alimentary phenotype; renal/urinary system phenotype; neoplasm; growth/size/body region phenotype; reproductive system 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); 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); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;chromatin remodeling;regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;spermatid development;nervous system development;negative regulation of cell population proliferation;negative regulation of cell growth;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;SWI/SNF complex;intracellular membrane-bounded organelle;intermediate filament cytoskeleton;npBAF complex;nBAF complex
• Molecular function: chromatin binding;transcription coactivator activity;helicase activity;protein binding;ATP binding;DNA-dependent ATPase activity;histone binding;transcription regulatory region DNA binding