Submissions for variant NM_014795.4(ZEB2):c.905G>A (p.Arg302Gln)

dbSNP: rs730881174

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000159444	SCV000209390	uncertain significance	not provided	2016-10-06	criteria provided, single submitter	clinical testing	The novel Arg302Gln missense change has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution of a positively charged Arginine residue with an uncharged Glutamine residue. In silico analysis predicts this variant is probably damaging to the protein structure/function. The variant occurs at a conserved position in the N-ZF domain of the protein; however, missense pathogenic variants in the ZEB2 gene are rare and have been identified in less than 2% of patients with Mowat-Wilson syndrome (Garavelli et al., 2009). Therefore, based on the currently available information, it is unclear whether Arg302Gln is a disease-causing variant or a rare benign variant.
Ambry Genetics	RCV002313010	SCV000848390	uncertain significance	Inborn genetic diseases	2016-12-19	criteria provided, single submitter	clinical testing	The p.R302Q variant (also known as c.905G>A), located in coding exon 6 of the ZEB2 gene, results from a G to A substitution at nucleotide position 905. The arginine at codon 302 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV001209725	SCV001381172	uncertain significance	Mowat-Wilson syndrome	2020-03-04	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ZEB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 181709). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glutamine at codon 302 of the ZEB2 protein (p.Arg302Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine.
Genome-Nilou Lab	RCV001209725	SCV002045633	uncertain significance	Mowat-Wilson syndrome	2021-11-07	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV001209725	SCV002505543	uncertain significance	Mowat-Wilson syndrome	2022-04-26	criteria provided, single submitter	clinical testing	This variant was identified as de novo (maternity and paternity confirmed)._x000D_ Criteria applied: PS2_SUP, PM2_SUP, PP2, PP3
Revvity Omics, Revvity	RCV001209725	SCV003826109	uncertain significance	Mowat-Wilson syndrome	2023-03-02	criteria provided, single submitter	clinical testing