SMARCC2

Chr 12AD

SWI/SNF related BAF chromatin remodeling complex subunit C2

Also known as: BAF170, CRACC2, CSS8, Rsc8

The protein is a core component of the SWI/SNF chromatin remodeling complex that uses ATP-dependent helicase activity to alter chromatin structure and regulate gene transcription. Loss-of-function mutations cause Coffin-Siris syndrome 8, an autosomal dominant neurodevelopmental disorder characterized by intellectual disability, distinctive facial features, and hypoplastic fifth fingernails and toenails. The gene is highly intolerant to loss-of-function variants, indicating haploinsufficiency as the disease mechanism.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.121 OMIM phenotype
Clinical SummarySMARCC2
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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.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 7.20
OE 0.05 (0.020.12)
Highly constrained

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

Missense Constraint
3.91Z-score
OE missense 0.59 (0.540.64)
416 obs / 708.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.05 (0.020.12)
00.351.4
Missense OE0.59 (0.540.64)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 3 / 66.2Missense obs/exp: 416 / 708.8Syn Z: 0.42
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongSMARCC2-related syndromic intellectual disability and developmental delayLOFAD
DN
0.2199th %ile
GOF
0.2298th %ile
LOF
0.86top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.12

Literature Evidence

LOFQuantitative RT-PCR in lymphocytes from patient 4 demonstrated an approximately 50% decrease in SMARCC2 mRNA compared to a control, suggesting haploinsufficiency through nonsense-mediated decay (NMD)PMID:30580808

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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