Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000642251 | SCV000763911 | uncertain significance | Mowat-Wilson syndrome | 2017-08-23 | 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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C35"). This variant has not been reported in the literature in individuals with ZEB2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glycine at codon 776 of the ZEB2 protein (p.Asp776Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. |
Neuberg Centre For Genomic Medicine, |
RCV000642251 | SCV005042790 | uncertain significance | Mowat-Wilson syndrome | criteria provided, single submitter | clinical testing | The missense c.2327A>Gp.Asp776Gly variant in ZEB2 gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The p.Asp776Gly variant is novel not in any individuals in both gnomAD Exomes and 1000 Genomes databases. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid change p.Asp776Gly in ZEB2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Asp at position 776 is changed to a Gly changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance VUS. |