ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.736A>G (p.Asn246Asp)

gnomAD frequency: 0.00002  dbSNP: rs1285224919
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000705271 SCV000834260 uncertain significance Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2023-08-25 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 241 of the WT1 protein (p.Asn241Asp). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with WT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 581447). 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001775148 SCV002012441 uncertain significance Wilms tumor 1 2022-05-02 criteria provided, single submitter clinical testing The WT1 c.721A>G (p.Asn241Asp) missense change has a maximum subpopulation frequency of 0.0065% gnomAD v2.1.1 (PM2_supporting; https://gnomad.broadinstitute.org/). In silico tools are inconclusive about the effect of this variant on protein function, and to our knowledge functional assays have not been performed. To our knowledge, this variant has not been reported in individuals with WT1-related conditions. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_supporting.
Baylor Genetics RCV003465633 SCV004208926 uncertain significance Drash syndrome 2023-09-27 criteria provided, single submitter clinical testing
GeneDx RCV004760745 SCV005372437 uncertain significance not provided 2023-06-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26496393, 8486616)

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