Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetic Services Laboratory, |
RCV000192778 | SCV000247332 | pathogenic | Weaver syndrome | 2014-03-27 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001778781 | SCV002015454 | likely pathogenic | not provided | 2023-02-12 | criteria provided, single submitter | clinical testing | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 22 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |
| Genesis Genoma Lab, |
RCV000192778 | SCV001885898 | likely pathogenic | Weaver syndrome | 2021-09-17 | no assertion criteria provided | clinical testing | The nucleotide variation EZH2: c.2187dup (p.Asp730Ter) results in the formation of a premature stop codon at the 730th aminoacid of the respective protein. It has been detected in a 4 year old patient with all the clinical characteristics of Weaver syndrome and was confirmed to be de novo. Most mutations in EZH2 gene are missesnse, however pathogenic nonsense and frameshift mutations have been reported at the 3' end of the gene, after the SET domain (PMID: 31724824, 28475857). The EZH2: c.2187dup (p.Asp730Ter) variant has been reported in a patient with Weaver syndrome in a poster presentation at the European Human Genetics Conference 2016 (Simsek et al. 2016). The detected nucleutide variant is not included in gnomAD database. The nucleotide variant EZH2: c.2187dup (p.Asp730Ter) is characterized as Likely Pathogenic according to ACMG guidelines. |