ClinVar Miner

Submissions for variant NM_014795.4(ZEB2):c.430T>A (p.Phe144Ile)

gnomAD frequency: 0.00001  dbSNP: rs1057518371
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413249 SCV000491950 uncertain significance not specified 2016-11-16 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ZEB2 gene. The F144I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant 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. The F144I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Phenylalanine are tolerated across species. Missense 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). Additionally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000799160 SCV000938812 uncertain significance Mowat-Wilson syndrome 2023-12-06 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 144 of the ZEB2 protein (p.Phe144Ile). This variant is present in population databases (no rsID available, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with ZEB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 373361). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Genome-Nilou Lab RCV000799160 SCV002045635 uncertain significance Mowat-Wilson syndrome 2021-11-07 criteria provided, single submitter clinical testing

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