SMARCC2

SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 2, the group of Myb/SANT domain containing|BAF complex|PBAF complex

Basic information

Region (hg38): 12:56162358-56189567

Links

ENSG00000139613 ∙ NCBI:6601 ∙ OMIM:601734 ∙ HGNC:11105 ∙ Uniprot:Q8TAQ2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Coffin-Siris syndrome (Supportive), mode of inheritance: AD
• Coffin-Siris syndrome 8 (Moderate), mode of inheritance: AD
• Coffin-Siris syndrome 8 (Strong), mode of inheritance: AD
• Coffin-Siris syndrome 8 (Definitive), mode of inheritance: AD
• Coffin-Siris syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Coffin-Siris syndrome 8	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	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	25590979; 27620904; 30580808

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMARCC2 gene.

• not provided (116 variants)
• Coffin-Siris syndrome 8 (46 variants)
• Inborn genetic diseases (25 variants)
• SMARCC2-related condition (8 variants)
• not specified (4 variants)
• SMARCC2-related BAFopathy (4 variants)
• See cases (3 variants)
• SMARCC2-related neurodevelopmental disorder (2 variants)
• Neurodevelopmental disorder (2 variants)
• Intellectual disability (1 variants)
• Neurodevelopmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMARCC2 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			2	15	5	22
missense	2	4	104	5		115
nonsense	1	4	2			7
start loss						0
frameshift	4	5	2			11
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)	3	3	4			10
splice region	1		3	2		6
non coding				1	16	17
Total	10	17	116	21	21

Highest pathogenic variant AF is 0.00000658

Variants in SMARCC2

This is a list of pathogenic ClinVar variants found in the SMARCC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-56163728-C-T			Likely benign (Aug 01, 2023)
12-56163757-T-G		Malignant tumor of prostate	Uncertain significance (-)
12-56163804-G-A			Benign (May 23, 2021)
12-56164372-C-T		Coffin-Siris syndrome 8	Uncertain significance (Sep 26, 2021)
12-56164373-G-A		SMARCC2-related disorder	Likely benign (Feb 01, 2023)
12-56164389-G-A		SMARCC2-related disorder	Conflicting classifications of pathogenicity (Feb 27, 2023)
12-56164400-C-A			Uncertain significance (Feb 10, 2023)
12-56164437-G-C			Uncertain significance (Jul 01, 2023)
12-56164451-C-T			Likely benign (Feb 01, 2023)
12-56164464-G-A		Inborn genetic diseases	Uncertain significance (Apr 06, 2022)
12-56164477-G-C		SMARCC2-related disorder	Likely benign (Feb 16, 2024)
12-56164534-G-C		Inborn genetic diseases	Likely benign (Dec 01, 2023)
12-56164537-C-T		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
12-56164567-G-C		Inborn genetic diseases	Likely benign (Feb 09, 2022)
12-56164575-AATGGGATG-A		Coffin-Siris syndrome 8	Likely pathogenic (Sep 12, 2022)
12-56164576-A-C			Uncertain significance (Dec 30, 2022)
12-56164589-T-TGGAGCAGGA		Coffin-Siris syndrome 8	Uncertain significance (Aug 14, 2020)
12-56164600-G-A			Uncertain significance (Sep 15, 2022)
12-56164603-G-A			Uncertain significance (Feb 22, 2023)
12-56164610-A-C			Likely benign (Oct 01, 2022)
12-56164613-C-T			Likely benign (May 01, 2023)
12-56164654-C-T		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
12-56164678-C-T			Uncertain significance (May 02, 2023)
12-56164680-G-A			Uncertain significance (Jan 31, 2023)
12-56164693-T-C		Inborn genetic diseases • SMARCC2-related disorder	Likely benign (Apr 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMARCC2	protein_coding	protein_coding	ENST00000267064	28	26585

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.36e-9	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.91	416	709	0.587	0.0000401	7923
Missense in Polyphen		5	25.281	0.19778		256
Synonymous	0.424	272	281	0.968	0.0000175	2415
Loss of Function	7.20	3	66.2	0.0453	0.00000360	732

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000353	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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 (PubMed:11018012). Can stimulate the ATPase activity of the catalytic subunit of these complexes (PubMed:10078207). May be required for CoREST dependent repression of neuronal specific gene promoters in non-neuronal cells (PubMed:12192000). 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). Critical regulator of myeloid differentiation, controlling granulocytopoiesis and the expression of genes involved in neutrophil granule formation (By similarity). {ECO:0000250|UniProtKB:Q6PDG5, ECO:0000269|PubMed:10078207, ECO:0000269|PubMed:11018012, ECO:0000269|PubMed:12192000, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}.
• Pathway: Thermogenesis - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Androgen Receptor Network in Prostate Cancer;Tumor suppressor activity of SMARCB1;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;the information processing pathway at the ifn beta enhancer;Generic Transcription Pathway;RNA Polymerase II Transcription;RMTs methylate histone arginines;Chromatin modifying enzymes;Glucocorticoid receptor regulatory network;Chromatin organization;chromatin remodeling by hswi/snf atp-dependent complexes;TNFalpha;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

• pRec: 0.138

Intolerance Scores

• loftool: 0.0106
• rvis_EVS: -1.66
• rvis_percentile_EVS: 2.71

Haploinsufficiency Scores

• pHI: 0.992
• hipred: Y
• hipred_score: 0.725
• ghis: 0.644

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smarcc2
• Phenotype: growth/size/body region phenotype; cellular 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); normal 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); embryo phenotype

Gene ontology

• Biological process: nucleosome disassembly;chromatin remodeling;regulation of transcription by RNA polymerase II;nervous system development;ATP-dependent chromatin remodeling;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated
• Cellular component: nuclear chromatin;nucleoplasm;SWI/SNF complex;protein-containing complex;npBAF complex;nBAF complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;transcription coactivator activity;protein binding;nucleosomal DNA binding