Rhabdoid tumor predisposition syndrome 2: genes and variants

Genes linked to Rhabdoid tumor predisposition syndrome 2

• SMARCA4: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4

  Its ATPase activity drives nucleosome remodeling in BAF-family complexes and thereby controls access to regulatory DNA. Germline pathogenic variants cause Coffin-Siris syndrome or rhabdoid-tumor predisposition, while somatic loss defines several aggressive cancers.

  10 disease-causing and 1,681 uncertain variants in SMARCA4 are linked to Rhabdoid tumor predisposition syndrome 2.

• SMARCB1: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1

  Within SWI/SNF complexes, it constrains oncogenic transcription and supports normal chromatin regulation. Biallelic tumor-cell inactivation is characteristic of malignant rhabdoid tumors, while germline variants predispose to rhabdoid tumors or schwannomatosis.

  0 disease-causing and 26 uncertain variants in SMARCB1 are linked to Rhabdoid tumor predisposition syndrome 2.

Known disease-causing variants in Rhabdoid tumor predisposition syndrome 2

Which prediction tools work for Rhabdoid tumor predisposition syndrome 2

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

• CATVariant: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 84 out of 100

Same protein, different disease

• SMARCA4-related BAFopathy is also caused by SMARCA4 variants; they fall mostly in different places as the Rhabdoid tumor predisposition syndrome 2 variants (5 disease-causing).

Diseases related to Rhabdoid tumor predisposition syndrome 2

• Coffin-Siris syndrome, also linked to SMARCA4 and SMARCB1
• Non-small cell lung carcinoma, also linked to SMARCA4
• Lung adenocarcinoma, also linked to SMARCA4
• NK-cell enteropathy, also linked to SMARCB1
• SMARCA4-related BAFopathy, also linked to SMARCA4
• Medulloblastoma, also linked to SMARCA4

Frequently asked questions

Which genes are linked to Rhabdoid tumor predisposition syndrome 2?

In CATVariant, Rhabdoid tumor predisposition syndrome 2 is linked to 2 analyzed proteins: SMARCA4 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4) and SMARCB1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1).

How many genetic variants are linked to Rhabdoid tumor predisposition syndrome 2?

1,776 variants: 10 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 1,707 are of uncertain significance or have conflicting reports.

Which uncertain variants in Rhabdoid tumor predisposition syndrome 2 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 Rhabdoid tumor predisposition syndrome 2?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.84, based on 9 disease-causing and 12 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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