ClinVar Miner

Submissions for variant NM_001282531.3(ADNP):c.2156dup (p.Tyr719Ter) (rs1135401808)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement,Assistance Publique Hopitaux de Paris RCV000170479 SCV000586774 pathogenic Helsmoortel-Van der Aa Syndrome 2017-01-06 criteria provided, single submitter clinical testing Intellectual disability, severe; antenatal cerebral ventriculomegaly; aggressive behaviour; small stature; probable neuropathy; stereotypies; dental disease; dysmorphism
GeneDx RCV000627402 SCV000748396 pathogenic not provided 2018-03-28 criteria provided, single submitter clinical testing The c.2156dupA variant in the ADNP gene has been reported previously as a de novo change in multiple individuals with autism spectrum disorder, intellectual disability and dysmorphic features (O'Roak et al., 2012, Helsmoortel et al., 2014). The c.2156dupA variant causes a frameshift starting with codon Tyrosine 719, changes this amino acid to a stop codon, and results in a nonsense variant denoted p.Tyr719X. This variant is predicted to result in protein truncation, as the last 384 amino acids are lost. Other loss-of-function variants have been reported downstream in the Human Gene Mutation Database. The c.2156dupA is not observed in large population cohorts (Lek et al., 2016). We interpret c.2156dupA as a pathogenic variant.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000170479 SCV000965718 pathogenic Helsmoortel-Van der Aa Syndrome 2015-01-01 criteria provided, single submitter clinical testing
Mendelics RCV000170479 SCV001141252 likely pathogenic Helsmoortel-Van der Aa Syndrome 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV000627402 SCV001415712 pathogenic not provided 2019-10-30 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the ADNP gene (p.Tyr719*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 384 amino acids of the ADNP protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Helsmoortel-van der Aa syndrome (PMID: 28221363, 28708303). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 190278). This variant has been reported to affect ADNP protein function (PMID: 29911927). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center RCV000170479 SCV001440879 pathogenic Helsmoortel-Van der Aa Syndrome 2019-01-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000627402 SCV001446524 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
OMIM RCV000170479 SCV000222906 pathogenic Helsmoortel-Van der Aa Syndrome 2015-03-12 no assertion criteria provided literature only
Diagnostic Laboratory, Strasbourg University Hospital RCV001249500 SCV001423490 pathogenic Intellectual disability 2017-12-01 no assertion criteria provided clinical testing
OMIM RCV000170479 SCV001481977 pathogenic Helsmoortel-Van der Aa Syndrome 2014-04-01 no assertion criteria provided literature only

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