ClinVar Genomic variation as it relates to human health
NM_001370100.5(ZMYND11):c.1798C>T (p.Arg600Trp)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001370100.5(ZMYND11):c.1798C>T (p.Arg600Trp)
Variation ID: 208648 Accession: VCV000208648.33
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10p15.3 10: 252459 (GRCh38) [ NCBI UCSC ] 10: 298399 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Sep 14, 2015 Apr 15, 2024 May 16, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001370100.5:c.1798C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357029.1:p.Arg600Trp missense NM_001202464.3:c.1636C>T NP_001189393.1:p.Arg546Trp missense NM_001202465.3:c.1543C>T NP_001189394.1:p.Arg515Trp missense NM_001202466.3:c.1633C>T NP_001189395.1:p.Arg545Trp missense NM_001330057.1:c.1747C>T NM_001330057.3:c.1747C>T NP_001316986.1:p.Arg583Trp missense NM_001370097.3:c.1798C>T NP_001357026.1:p.Arg600Trp missense NM_001370098.2:c.1798C>T NP_001357027.1:p.Arg600Trp missense NM_001370099.2:c.1798C>T NP_001357028.1:p.Arg600Trp missense NM_001370101.2:c.1798C>T NP_001357030.1:p.Arg600Trp missense NM_001370102.2:c.1798C>T NP_001357031.1:p.Arg600Trp missense NM_001370103.2:c.1636C>T NP_001357032.1:p.Arg546Trp missense NM_001370104.2:c.1636C>T NP_001357033.1:p.Arg546Trp missense NM_001370105.2:c.1636C>T NP_001357034.1:p.Arg546Trp missense NM_001370106.2:c.1636C>T NP_001357035.1:p.Arg546Trp missense NM_001370107.2:c.1636C>T NP_001357036.1:p.Arg546Trp missense NM_001370108.2:c.1636C>T NP_001357037.1:p.Arg546Trp missense NM_001370109.2:c.1636C>T NP_001357038.1:p.Arg546Trp missense NM_001370110.2:c.1543C>T NP_001357039.1:p.Arg515Trp missense NM_001370111.2:c.1633C>T NP_001357040.1:p.Arg545Trp missense NM_001370112.2:c.1747C>T NP_001357041.1:p.Arg583Trp missense NM_001370113.2:c.1705C>T NP_001357042.1:p.Arg569Trp missense NM_001370114.2:c.1705C>T NP_001357043.1:p.Arg569Trp missense NM_001370115.2:c.1795C>T NP_001357044.1:p.Arg599Trp missense NM_001370116.2:c.1732C>T NP_001357045.1:p.Arg578Trp missense NM_001370117.2:c.1729C>T NP_001357046.1:p.Arg577Trp missense NM_001370118.2:c.1678C>T NP_001357047.1:p.Arg560Trp missense NM_001370119.2:c.1651C>T NP_001357048.1:p.Arg551Trp missense NM_001370120.2:c.1570C>T NP_001357049.1:p.Arg524Trp missense NM_001370121.2:c.1516C>T NP_001357050.1:p.Arg506Trp missense NM_001370122.2:c.1492C>T NP_001357051.1:p.Arg498Trp missense NM_001370123.2:c.1441C>T NP_001357052.1:p.Arg481Trp missense NM_001370124.3:c.1327C>T NP_001357053.1:p.Arg443Trp missense NM_006624.7:c.1798C>T NP_006615.2:p.Arg600Trp missense NR_163254.2:n.1829C>T non-coding transcript variant NC_000010.11:g.252459C>T NC_000010.10:g.298399C>T NG_029960.1:g.122995C>T - Protein change
- R600W, R481W, R498W, R506W, R515W, R569W, R577W, R545W, R551W, R578W, R560W, R599W, R443W, R524W, R546W, R583W
- Other names
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- Canonical SPDI
- NC_000010.11:252458:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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ZMYND11 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
205 | 335 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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Nov 20, 2014 | RCV000190655.3 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 20, 2023 | RCV000358614.19 | |
Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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May 16, 2023 | RCV001004105.12 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 1, 2019 | RCV001255412.2 | |
not provided (1) |
no classification provided
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- | RCV001844080.2 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Nov 23, 2022 | RCV003407691.4 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jan 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 30
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV001162833.1
First in ClinVar: Feb 29, 2020 Last updated: Feb 29, 2020 |
Sex: female
Tissue: blood
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Pathogenic
(Nov 01, 2019)
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criteria provided, single submitter
Method: clinical testing
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Global developmental delay
Affected status: yes
Allele origin:
de novo
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Génétique des Maladies du Développement, Hospices Civils de Lyon
Accession: SCV001431812.1
First in ClinVar: Sep 14, 2020 Last updated: Sep 14, 2020 |
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Pathogenic
(Jun 24, 2021)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 30
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001950014.1
First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(Oct 02, 2021)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 30
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002012118.1
First in ClinVar: Nov 11, 2021 Last updated: Nov 11, 2021 |
Comment:
Same nucleotide change resulting in same amino acid change has been previously reported multiple times as de novoo in similarly affected unrelated individuals ( PMID: … (more)
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. (less)
Clinical Features:
Abnormal facial shape (present) , Cryptorchidism (present) , Inguinal hernia (present) , External ear malformation (present) , Hypothyroidism (present) , Global developmental delay (present) , … (more)
Abnormal facial shape (present) , Cryptorchidism (present) , Inguinal hernia (present) , External ear malformation (present) , Hypothyroidism (present) , Global developmental delay (present) , Intraventricular hemorrhage (present) , Patent foramen ovale (present) , Failure to thrive (present) (less)
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Pathogenic
(Nov 20, 2014)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV000244095.6
First in ClinVar: Sep 14, 2015 Last updated: Jan 07, 2023 |
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Muscular hypotonia (present) , Failure to thrive (present) , Microcephaly (present) , Hirsutism (present) , Wide nasal bridge (present) , Inguinal hernia (present) , Oral … (more)
Muscular hypotonia (present) , Failure to thrive (present) , Microcephaly (present) , Hirsutism (present) , Wide nasal bridge (present) , Inguinal hernia (present) , Oral aversion (present) , Oligohydramnios (present) , Synophrys (present) , Generalized hirsutism (present) , Prominent fingertip pads (present) , Abnormality of the eye (present) , Intellectual disability, profound (present) , Intellectual disability (present) (less)
Sex: male
Ethnicity/Population group: Asian/Korean
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Global developmental delay (present) , Muscular hypotonia (present) , Short stature (present) , Feeding difficulties (present) , Aspiration (present) , Gastroesophageal reflux (present) , Sacral … (more)
Global developmental delay (present) , Muscular hypotonia (present) , Short stature (present) , Feeding difficulties (present) , Aspiration (present) , Gastroesophageal reflux (present) , Sacral dimple (present) , Micrognathia (present) , Choanal atresia (present) , Sleep apnea (present) , Low-set ears (present) , Narrow palpebral fissure (present) , Hypertelorism (present) , Epicanthus (present) , Deeply set eye (present) , Short nose (present) , Broad nasal tip (present) , Short neck (present) , Hypoplastic nipples (present) , Wide intermamillary distance (present) , Tapered finger (present) , Tachycardia (present) , Patent ductus arteriosus (present) (less)
Sex: male
Ethnicity/Population group: Hispanic/Caucasian
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Pathogenic
(Sep 12, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000330043.8
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
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; … (more)
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) (less)
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Likely pathogenic
(Dec 23, 2019)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 30
Affected status: yes
Allele origin:
germline
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Laboratoire de Génétique Moléculaire, CHU Bordeaux
Accession: SCV003836669.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Pathogenic
(May 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 30
Affected status: yes
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV004013219.1
First in ClinVar: Jul 22, 2023 Last updated: Jul 22, 2023 |
Comment:
PS2, PS4, PM2, PP2, PP3
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Likely pathogenic
(Nov 23, 2022)
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criteria provided, single submitter
Method: clinical testing
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ZMYND11-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004115504.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
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 … (more)
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. (less)
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Pathogenic
(Mar 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV004295633.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
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 … (more)
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. (less)
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Pathogenic
(Aug 01, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001961198.14
First in ClinVar: Oct 07, 2021 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(May 31, 2019)
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no assertion criteria provided
Method: research
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Intellectual disability, autosomal dominant 30
Affected status: yes
Allele origin:
de novo
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Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital
Accession: SCV001482362.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
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not provided
(-)
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no classification provided
Method: phenotyping only
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Neurodevelopmental disorder
Affected status: yes
Allele origin:
de novo
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GenomeConnect - Brain Gene Registry
Accession: SCV002103320.1
First in ClinVar: Mar 12, 2022 Last updated: Mar 12, 2022 |
Comment:
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 … (more)
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/. (less)
Clinical Features:
Decreased fetal movement (present) , Short stature (present) , Failure to thrive (present) , Decreased response to growth hormone stimulation test (present) , Hyperthyroidism (present) … (more)
Decreased fetal movement (present) , Short stature (present) , Failure to thrive (present) , Decreased response to growth hormone stimulation test (present) , Hyperthyroidism (present) , Abnormal facial shape (present) , Abnormality of the nose (present) , Abnormal skull morphology (present) , Oral-pharyngeal dysphagia (present) , Abnormality of eye movement (present) , Abnormal optic nerve morphology (present) , Sensorineural hearing loss disorder (present) , Hearing impairment (present) , Abnormality of the nervous system (present) , Cognitive impairment (present) , Abnormality of coordination (present) , EEG abnormality (present) , Encephalopathy (present) , Hypertonia (present) , Movement disorder (present) , Seizure (present) , Autistic behavior (present) , Joint hypermobility (present) , Abnormal muscle physiology (present) , Abnormality of the musculature of the limbs (present) , Abnormality of the musculature (present) , Feeding difficulties (present) , Abnormal esophagus morphology (present) , Abnormal stomach morphology (present) , Gastrointestinal dysmotility (present) , Abnormal large intestine morphology (present) , Recurrent infections (present) (less)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: female
Method: Sanger Sequencing
Testing laboratory: GeneDx
Date variant was reported to submitter: 2019-01-30
Testing laboratory interpretation: Pathogenic
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Untangling neurodevelopmental disorders in the adulthood: a movement disorder is the clue. | Indelicato E | Orphanet journal of rare diseases | 2022 | PMID: 35172867 |
Phenotype comparison confirms ZMYND11 as a critical gene for 10p15.3 microdeletion syndrome. | Tumiene B | Journal of applied genetics | 2017 | PMID: 28933030 |
Refining the role of de novo protein-truncating variants in neurodevelopmental disorders by using population reference samples. | Kosmicki JA | Nature genetics | 2017 | PMID: 28191890 |
Mutations in HECW2 are associated with intellectual disability and epilepsy. | Halvardson J | Journal of medical genetics | 2016 | PMID: 27334371 |
A de novo mutation in ZMYND11, a candidate gene for 10p15.3 deletion syndrome, is associated with syndromic intellectual disability. | Cobben JM | European journal of medical genetics | 2014 | PMID: 25281490 |
Text-mined citations for rs797044854 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.