ClinVar Miner

Submissions for variant NM_018669.6(WDR4):c.586G>A (p.Val196Met)

gnomAD frequency: 0.00061  dbSNP: rs141906425
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002919041 SCV003262121 uncertain significance not provided 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 196 of the WDR4 protein (p.Val196Met). This variant is present in population databases (rs141906425, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with WDR4-related conditions. ClinVar contains an entry for this variant (Variation ID: 2053306). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on WDR4 protein function. 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.
Ambry Genetics RCV002922400 SCV003688395 uncertain significance Inborn genetic diseases 2022-01-04 criteria provided, single submitter clinical testing The c.586G>A (p.V196M) alteration is located in exon 6 (coding exon 6) of the WDR4 gene. This alteration results from a G to A substitution at nucleotide position 586, causing the valine (V) at amino acid position 196 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003926533 SCV004743150 likely benign WDR4-related disorder 2022-05-02 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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