ClinVar Miner

Submissions for variant NM_025000.4(DCAF17):c.724G>A (p.Ala242Thr)

gnomAD frequency: 0.00059  dbSNP: rs149650431
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000513204 SCV000608988 uncertain significance not provided 2017-06-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001130165 SCV001289735 uncertain significance Woodhouse-Sakati syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV001130165 SCV001416906 uncertain significance Woodhouse-Sakati syndrome 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 242 of the DCAF17 protein (p.Ala242Thr). This variant is present in population databases (rs149650431, gnomAD 0.2%), 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 DCAF17-related conditions. ClinVar contains an entry for this variant (Variation ID: 444538). 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) performed at Invitae indicates that this missense variant is not expected to disrupt DCAF17 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.
GeneDx RCV000513204 SCV002050503 uncertain significance not provided 2024-05-12 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences RCV003915425 SCV004728651 likely benign DCAF17-related disorder 2023-03-16 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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