SMARCC2

Chr 12AD

SWI/SNF related BAF chromatin remodeling complex subunit C2

Also known as: BAF170, CRACC2, CSS8, Rsc8

NCBI Gene: 6601ENSG00000139613UniProt: Q8TAQ2

The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and contains a predicted leucine zipper motif typical of many transcription factors. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Coffin-Siris syndrome 8MIM #618362
AD
437
ClinVar variants
62
Pathogenic / LP
1.00
pLI score· haploinsufficient
2
Active trials
Clinical Summary— SMARCC2
🧬
Gene-Disease Validity (ClinGen)
Coffin-Siris syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
62 Pathogenic / Likely Pathogenic· 290 VUS of 437 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.12LOEUF
pLI 1.000
Z-score 7.20
OE 0.05 (0.02–0.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.91Z-score
OE missense 0.59 (0.54–0.64)
416 obs / 708.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.02–0.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.59 (0.54–0.64)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 3 / 66.2Missense obs/exp: 416 / 708.8Syn Z: 0.42

ClinVar Variant Classifications

437 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic33
VUS290
Likely Benign56
Benign21
Conflicting8
29
Pathogenic
33
Likely Pathogenic
290
VUS
56
Likely Benign
21
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
3
12
0
29
Likely Pathogenic
14
7
12
0
33
VUS
8
255
23
4
290
Likely Benign
0
20
5
31
56
Benign
0
1
17
3
21
Conflicting
—8
Total362866938437

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SMARCC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SMARCC2-related syndromic intellectual disability and developmental delay

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Coffin-Siris syndrome 8

MIM #618362

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — SMARCC2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome.
Vasko A et al.·Genes (Basel)
2021
Elucidating the clinical and molecular spectrum of SMARCC2-associated NDD in a cohort of 65 affected individuals.
Bosch E et al.·Genet Med
2023Cohort
Identification and functional analysis of a novel SMARCC2 splicing variant in a family with syndromic neurodevelopmental disorder.
Li M et al.·Orphanet J Rare Dis
2025Case report
Delineation of the adult phenotype of Coffin-Siris syndrome in 35 individuals.
Schmetz A et al.·Hum Genet
2024
Expanding the phenotype associated with SMARCC2 variants: a fetus with tetralogy of Fallot.
Sun H et al.·BMC Med Genomics
2022Case report
De Novo SMARCC2 Variant in a Chinese Woman with Coffin-Siris Syndrome 8: a Case Report with Mild Intellectual Disability and Endocrinopathy.
Yi S et al.·J Mol Neurosci
2022Case report
Identification of selective SWI/SNF dependencies in enzalutamide-resistant prostate cancer.
Gokbayrak B et al.·Commun Biol
2025
Further supporting SMARCC2-related neurodevelopmental disorder through exome analysis and reanalysis in two patients.
Li D et al.·Am J Med Genet A
2022Case report
Clinical and Genetic Analysis of SMARCC2-Related Diseases in Three Chinese Patients.
Ou S et al.·Mol Genet Genomic Med
2026Case report
SWI/SNF Alterations in Squamous Bladder Cancers.
Achenbach F et al.·Genes (Basel)
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10
Solid Tumor MalignanciesClear Cell Endometrial CarcinomaOvarian Cancer

Efficacy and Safety of the Valemetostat in Patients With Selected Solid Tumors.

NOT YET RECRUITING
NCT07303387Phase PHASE2Gustave Roussy, Cancer Campus, Grand ParisStarted 2026-02-28
Valemetostat Tosylate

External Resources

Links to major genomics databases and tools