Submissions for variant NM_014795.4(ZEB2):c.904C>T (p.Arg302Ter)

dbSNP: rs587784571

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000148007	SCV000195505	pathogenic	Mowat-Wilson syndrome	2013-02-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000167554	SCV000209418	pathogenic	not provided	2024-08-07	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29093530, 25525159, 19842203, 24715670, 28096981, 32005694, 29655203, 16053902, 17958891, 31104665, 36403551, 33057194, 36406119, 35982159, 15121779)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000148007	SCV001414045	pathogenic	Mowat-Wilson syndrome	2024-06-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg302*) in the ZEB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ZEB2 are known to be pathogenic (PMID: 16053902). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Mowat-Wilson syndrome (PMID: 15121779, 19842203). ClinVar contains an entry for this variant (Variation ID: 160329). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000148007	SCV002020931	pathogenic	Mowat-Wilson syndrome	2021-04-09	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000148007	SCV002045652	pathogenic	Mowat-Wilson syndrome	2021-11-07	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000148007	SCV003761408	pathogenic	Mowat-Wilson syndrome	2023-01-25	criteria provided, single submitter	curation	The heterozygous p.Arg302Ter variant in ZEB2 was identified by our study in one individual with periventricular heterotopia, agenesis of the corpus callosum, and seizures. Trio exome analysis showed this variant to be de novo. The p.Arg302Ter variant in ZEB2 has been previously reported in at least 4 unrelated individuals with Mowat Wilson syndrome (PMID: 28096981, PMID: 29093530, PMID: 15121779, PMID: 19842203). The number of reported affected individuals with this variant is slightly greater than expected compared to non-affected individuals with this variant. This variant was found to be de novo in 2 individuals with confirmed paternity and maternity (PMID: 28096981, PMID: 29093530). This variant has also been reported in ClinVar (Variation ID: 160329) and has been interpreted as pathogenic by multiple submitters. This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 302, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the ZEB2 gene is an established disease mechanism in autosomal dominant Mowat Wilson syndrome. In summary, this variant meets criteria to be classified as pathogenic for Mowat Wilson syndrome. ACMG/AMP Criteria applied: PVS1, PS2, PS4_Moderate, PM2_Supporting (Richards 2015).
Fulgent Genetics, Fulgent Genetics	RCV000148007	SCV005652933	likely pathogenic	Mowat-Wilson syndrome	2024-04-30	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000167554	SCV000218433	pathogenic	not provided	2015-01-30	no assertion criteria provided	clinical testing
Molecular Genetics Laboratory, Children's Mercy Hospital and Clinics	RCV000148007	SCV000221244	pathogenic	Mowat-Wilson syndrome	2015-03-02	no assertion criteria provided	clinical testing