ClinVar Miner

Submissions for variant NM_021008.4(DEAF1):c.646A>G (p.Lys216Glu)

dbSNP: rs1590017652
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000994533 SCV001148127 uncertain significance not provided 2017-11-01 criteria provided, single submitter clinical testing
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes RCV000994533 SCV001334352 uncertain significance not provided 2020-02-12 criteria provided, single submitter clinical testing
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine RCV003127573 SCV003804017 likely pathogenic Developmental disorder 2022-02-07 criteria provided, single submitter clinical testing
Laboratoire de Génétique Moléculaire, CHU Bordeaux RCV003148908 SCV003836687 likely pathogenic Intellectual disability-epilepsy-extrapyramidal syndrome 2020-08-10 criteria provided, single submitter clinical testing
Invitae RCV000994533 SCV004535438 pathogenic not provided 2023-11-12 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 216 of the DEAF1 protein (p.Lys216Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant DEAF1-related neurodevelopmental disorder (PMID: 30923367). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 806589). 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 expected to disrupt DEAF1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects DEAF1 function (PMID: 30923367). This variant disrupts the p.Lys216 amino acid residue in DEAF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30923367). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV003148908 SCV004805994 likely pathogenic Intellectual disability-epilepsy-extrapyramidal syndrome 2024-03-25 criteria provided, single submitter clinical testing

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