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

gnomAD frequency: 0.00001  dbSNP: rs773618224

Total submissions: 13

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
Invitae	RCV001090402	SCV001576800	pathogenic	not provided	2021-01-27	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with PRUNE1-related neurodevelopmental conditions (PMID: 26539891, 28334956, 29797509). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 402131). This variant is present in population databases (rs773618224, ExAC 0.02%). This sequence change replaces aspartic acid with asparagine at codon 106 of the PRUNE1 protein (p.Asp106Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine.
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 Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine	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.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000490535	SCV004801175	pathogenic	Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies	2024-03-14	criteria provided, single submitter	research
OMIM	RCV000490535	SCV000577901	pathogenic	Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies	2022-10-21	no assertion criteria provided	literature only