Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetics and Molecular Pathology, |
RCV003447716 | SCV004175384 | pathogenic | Familial meningioma | 2022-11-24 | criteria provided, single submitter | clinical testing | The SMARCE1 c.587del variant is classified as PATHOGENIC (PVS1, PM2, PP4) This SMARCE1 c.587del variant is located in exon 8/11 and is predicted to cause a shift in the reading frame at codon 196, leading to the introduction of a premature stop codon (PVS1). This variant is absent from population databases (PM2). The clinical features of this case are highly specific for the genes tested as part of this panel and this patient has a well-defined syndrome with little overlap with other clinical presentations (PP4). This variant has not been reported in dbSNP, ClinVar or HGMD. |
| Victorian Clinical Genetics Services, |
RCV003447716 | SCV005087247 | pathogenic | Familial meningioma | 2023-12-21 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with susceptibility to familial meningioma (MIM#607174) and Coffin-Siris syndrome 5 (MIM#616938), respectively (PMIDs: 23556151, 26803492, 37164167). Dominant negative has also been reported for the latter (PMID: 23556151). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other premature termination variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Many germline NMD-predicted variants in this gene have been reported in families with clear cell meningioma (PMID: 37164167). These variants have also been reported as likely pathogenic/pathogenic in the context of familial meningioma or hereditary cancer-predisposing syndrome (ClinVar). (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. It has been reported in a child with an unspecified cancer in the central nervous system (PMID: 33020650). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |