Submissions for variant NM_001370100.5(ZMYND11):c.1798C>T (p.Arg600Trp)

dbSNP: rs797044854

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000190655	SCV000244095	pathogenic	Inborn genetic diseases	2014-11-20	criteria provided, single submitter	clinical testing
GeneDx	RCV000358614	SCV000330043	pathogenic	not provided	2022-09-12	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27626064, 25281490, 27334371, 28933030, 28135719, 28191890, 23372760, 33098801, 34006472, 31785789, 35172867)
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV001004105	SCV001162833	pathogenic	Intellectual disability, autosomal dominant 30	2020-01-23	criteria provided, single submitter	clinical testing
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV001255412	SCV001431812	pathogenic	Global developmental delay	2019-11-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV001004105	SCV001950014	pathogenic	Intellectual disability, autosomal dominant 30	2021-06-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000358614	SCV001961198	pathogenic	not provided	2021-08-01	criteria provided, single submitter	clinical testing
3billion	RCV001004105	SCV002012118	pathogenic	Intellectual disability, autosomal dominant 30	2021-10-02	criteria provided, single submitter	clinical testing	Same nucleotide change resulting in same amino acid change has been previously reported multiple times as de novoo in similarly affected unrelated individuals ( PMID: 28191890, 28933030, 27334371, PS2, PS4). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). It is not observed in the gnomAD v2.1.1 dataset (PM2). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.843, 3Cnet: 0.995, PP3). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Laboratoire de Génétique Moléculaire, CHU Bordeaux	RCV001004105	SCV003836669	likely pathogenic	Intellectual disability, autosomal dominant 30	2019-12-23	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV001004105	SCV004013219	pathogenic	Intellectual disability, autosomal dominant 30	2023-05-16	criteria provided, single submitter	clinical testing	PS2, PS4, PM2, PP2, PP3
PreventionGenetics, part of Exact Sciences	RCV003407691	SCV004115504	likely pathogenic	ZMYND11-related disorder	2022-11-23	criteria provided, single submitter	clinical testing	The ZMYND11 c.1798C>T variant is predicted to result in the amino acid substitution p.Arg600Trp. This is a recurrent de novo variant reported in individuals with Intellectual disability (Cobben et al. 2014. PubMed ID: 25281490; Fam7, Tables S1 and S2, referred to as Chr10:298399C>T, Halvardson et al. 2016. PubMed ID: 27334371; Table S1, referred to as Chr10:298399C>T, McRae et al. 2017. PubMed ID: 28135719; Table S2, Kosmicki et al. 2017. PubMed ID: 28191890; Turner et al. 2019. PubMed ID: 31785789; Table S2, Zech et al. 2020. PubMed ID: 33098801; Table S2, Fan et al. 2021. PubMed ID: 34006472). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic.
Invitae	RCV000358614	SCV004295633	pathogenic	not provided	2023-03-20	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 600 of the ZMYND11 protein (p.Arg600Trp). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 208648). This missense change has been observed in individual(s) with developmental delay (PMID: 25281490, 35172867). In at least one individual the variant was observed to be de novo.
Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital	RCV001004105	SCV001482362	pathogenic	Intellectual disability, autosomal dominant 30	2019-05-31	no assertion criteria provided	research
GenomeConnect - Brain Gene Registry	RCV001844080	SCV002103320	not provided	Neurodevelopmental disorder		no assertion provided	phenotyping only	Variant interpreted as Pathogenic and reported on 43495 by lab or GTR ID 26957. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator John Constantino MD PhD from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.