ClinVar Miner

Submissions for variant NM_021008.4(DEAF1):c.671G>A (p.Arg224Gln)

gnomAD frequency: 0.00001  dbSNP: rs1415420832
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine RCV003127670 SCV003804018 likely pathogenic Autism spectrum disorder criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004528401 SCV004110323 likely pathogenic DEAF1-related disorder 2023-12-29 criteria provided, single submitter clinical testing The DEAF1 c.671G>A variant is predicted to result in the amino acid substitution p.Arg224Gln. This variant was reported as an inherited biallelic variant in an individual with autosomal recessive psychomotor development disorder (Table S7, Nabais Sá et al. 2019. PubMed ID: 30923367) and found in another individual with autism spectrum disorder, who inherited this variant from his mother, but no clinical information for his mother was provided (Husson et al. 2020. PubMed ID: 32094338). In addition, a different variant affecting the same amino acid (p.Arg224Trp) was reported as a de novo variant in one individual with autism spectrum disorder (Table S1, Nabais Sá et al. 2019. PubMed ID: 30923367). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. This variant is interpreted as likely pathogenic.
Invitae RCV003718379 SCV004511913 uncertain significance not provided 2023-05-16 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 915957). This missense change has been observed in individual(s) with autosomal recessive DEAF1-related conditions (PMID: 30923367). It has also been observed to segregate with disease in related individuals. This variant has been reported in individual(s) with autosomal dominant DEAF1-related conditions (PMID: 32094338); however, the role of the variant in this condition is currently unclear. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 224 of the DEAF1 protein (p.Arg224Gln). 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 DEAF1 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on DEAF1 function (PMID: 30923367).
OMIM RCV001171489 SCV001334291 pathogenic Intellectual disability-epilepsy-extrapyramidal syndrome 2020-06-01 no assertion criteria provided literature only

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