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

dbSNP: rs1590017652

Total submissions: 6

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