| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Schwannoma v0.13 | SMARCA4 | Zornitza Stark Marked gene: SMARCA4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Schwannoma v0.13 | SMARCA4 | Zornitza Stark Gene: smarca4 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Schwannoma v0.12 | SMARCA4 |
Chirag Patel gene: SMARCA4 was added gene: SMARCA4 was added to Schwannoma. Sources: Expert Review,Literature Mode of inheritance for gene: SMARCA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SMARCA4 were set to PMID: 36786840 Phenotypes for gene: SMARCA4 were set to Schwannoma, MONDO:0002546; Rhabdoid tumor predisposition syndrome 2, MONDO:0013224; Rhabdoid tumor predisposition syndrome 2, MIM#613325 Review for gene: SMARCA4 was set to RED Added comment: ClinGen definitive for RTPS2 1 family with 3 affected individuals with adult-onset schwannomas (2/3), glioblastoma (1/3), and malignant peripheral nerve sheath tumour (1/3). Whole-genome sequencing in proband identified a variant in SMARCA4 gene ([c.1752_1755del, p.(Lys585Argfs*27). In the schwannomas, immunohistochemical (IHC) staining showed loss of BRG1 (SMARCA4) expression in 80–90% of cells and loss of INI1 (SMARCB1) in the complementary 10–20% of cells in all 5 schwannomas but complete retention of BRG1 and INI1 in the glioblastoma. Whole exome sequencing (WES) of DNA from proband's blood, mother’s normal skin, all 5 schwannomas and the glioblastoma, confirmed the presence of the truncating SMARCA4 LPV in all samples. LOH was observed at the SMARCA4 locus, extending to 12–23 Mb of Chromosome 19p (Chr19p) in all schwannomas, but not in the glioblastoma. No LOH of Chr22q was detected in the schwannomas. The germline SMARCA4 variant was also detected in proband's maternal grandfather’s MPNST in a heterozygous state. Sources: Expert Review, Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||