ClinVar Miner

Submissions for variant NM_021222.3(PRUNE1):c.316G>A (p.Asp106Asn)

gnomAD frequency: 0.00001  dbSNP: rs773618224
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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000454333 SCV000537906 likely pathogenic Abnormal brain morphology criteria provided, single submitter research There are 3 more families with similar phenotype
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000490535 SCV000680349 pathogenic Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies 2020-01-16 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000490535 SCV000966201 pathogenic Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies 2018-05-09 criteria provided, single submitter clinical testing Observed as a homozygote.
CeGaT Center for Human Genetics Tuebingen RCV001090402 SCV001245938 pathogenic not provided 2018-05-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000490535 SCV001251444 pathogenic Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies 2019-10-29 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000490535 SCV001251858 pathogenic Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies 2020-05-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001090402 SCV001576800 pathogenic not provided 2024-11-18 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 106 of the PRUNE1 protein (p.Asp106Asn). This variant is present in population databases (rs773618224, gnomAD 0.02%). This missense change has been observed in individual(s) with PRUNE1-related neurodevelopmental conditions (PMID: 26539891, 28334956, 29797509). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 402131). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PRUNE1 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001090402 SCV001762256 pathogenic not provided 2021-06-17 criteria provided, single submitter clinical testing
Centogene AG - the Rare Disease Company RCV000490535 SCV002059724 pathogenic Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies 2018-01-09 criteria provided, single submitter clinical testing
Provincial Medical Genetics Program of British Columbia, University of British Columbia RCV000490535 SCV002320834 pathogenic Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies 2022-01-01 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000490535 SCV004047534 pathogenic Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies criteria provided, single submitter clinical testing The missense variant c.316G>A (p.Asp106Asn) in PRUNE1 gene has been reported to be homozygous in several individuals with syndromic intellectual disability (Karaca E et.al.,2015). Experimental studies show that missense change affect PRUNE1 function (Zollo M et.al .,2017). This variant has been reported to the ClinVar database as Pathogenic/Likely Pathogenic. The p.Asp106Asn variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.00005177% is reported in gnomAD. The amino acid Asp at position 106 is changed to a Asn changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Pathogenic.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV000490535 SCV004801175 pathogenic Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies 2024-03-14 criteria provided, single submitter research
Juno Genomics, Hangzhou Juno Genomics, Inc RCV000490535 SCV005418519 pathogenic Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies criteria provided, single submitter clinical testing PM2_Supporting+PS3_Supporting+PM3_VeryStrong
OMIM RCV000490535 SCV000577901 pathogenic Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies 2022-10-21 no assertion criteria provided literature only

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