Nicolaides-Baraitser syndrome: genes and variants

Genes linked to Nicolaides-Baraitser syndrome

• SMARCA2: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2

  It provides ATP-dependent nucleosome remodeling activity to selected SWI/SNF complexes and helps control transcriptional access to chromatin. Heterozygous pathogenic variants cause Nicolaides-Baraitser syndrome or, through distinct mechanisms, blepharophimosis-intellectual-disability syndrome.

  50 disease-causing and 57 uncertain variants in SMARCA2 are linked to Nicolaides-Baraitser syndrome.

Where Nicolaides-Baraitser syndrome variants cluster

• SMARCA2 Helicase C-terminal (positions 1054–1216): 24 of 50 disease-causing changes, 4.7× more than its size predicts.
• SMARCA2 DEGH box (positions 851–854): 3 of 50 disease-causing changes, 23.9× more than its size predicts.

Known disease-causing variants in Nicolaides-Baraitser syndrome

Which prediction tools work for Nicolaides-Baraitser syndrome

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 98 out of 100
• EVE: 98 out of 100
• SIFT: 95 out of 100
• MutPred2: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Blepharophimosis-impaired intellectual development syndrome is also caused by SMARCA2 variants; they fall partly in the same places as the Nicolaides-Baraitser syndrome variants (8 disease-causing).
• SMARCA2-related BAFopathy is also caused by SMARCA2 variants; they fall in the same places as the Nicolaides-Baraitser syndrome variants (7 disease-causing).

Diseases related to Nicolaides-Baraitser syndrome

• Blepharophimosis-impaired intellectual development syndrome, also linked to SMARCA2
• SMARCA2-related BAFopathy, also linked to SMARCA2
• Pituitary stalk interruption syndrome, also linked to SMARCA2

Frequently asked questions

Which genes are linked to Nicolaides-Baraitser syndrome?

In CATVariant, Nicolaides-Baraitser syndrome is linked to 1 analyzed protein: SMARCA2 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2).

How many genetic variants are linked to Nicolaides-Baraitser syndrome?

126 variants: 50 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 57 are of uncertain significance or have conflicting reports.

Which uncertain variants in Nicolaides-Baraitser syndrome look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Nicolaides-Baraitser syndrome?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.98, based on 42 disease-causing and 86 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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