ClinVar Genomic variation as it relates to human health
NM_001029896.2(WDR45):c.397C>T (p.Arg133Ter)
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_001029896.2(WDR45):c.397C>T (p.Arg133Ter)
Variation ID: 212592 Accession: VCV000212592.44
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xp11.23 X: 49076469 (GRCh38) [ NCBI UCSC ] X: 48934128 (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 Oct 5, 2015 Apr 15, 2024 Apr 26, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001029896.2:c.397C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001025067.1:p.Arg133Ter nonsense NM_007075.4:c.400C>T NP_009006.2:p.Arg134Ter nonsense NC_000023.11:g.49076469G>A NC_000023.10:g.48934128G>A NG_033004.2:g.29702C>T - Protein change
- R134*, R133*
- Other names
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- Canonical SPDI
- NC_000023.11:49076468:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- Unknown function
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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
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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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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WDR45 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh38 GRCh37 |
361 | 645 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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
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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 (2) |
criteria provided, multiple submitters, no conflicts
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Apr 20, 2023 | RCV000413483.20 | |
Pathogenic/Likely pathogenic (7) |
criteria provided, multiple submitters, no conflicts
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Apr 26, 2023 | RCV000477948.22 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 1, 2017 | RCV000679876.4 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
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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
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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
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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
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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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Likely pathogenic
(Jul 07, 2015)
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criteria provided, single submitter
Method: clinical testing
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Neurodegeneration with brain iron accululation 5
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000249437.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
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Pathogenic
(Mar 06, 2018)
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criteria provided, single submitter
Method: clinical testing
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Neurodegeneration with brain iron accumulation 5
(X-linked inheritance)
Affected status: yes
Allele origin:
de novo
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Génétique des Maladies du Développement, Hospices Civils de Lyon
Accession: SCV001164217.1
First in ClinVar: Mar 01, 2020 Last updated: Mar 01, 2020 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Neurodegeneration with brain iron accumulation 5
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
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Consultorio y Laboratorio de Neurogenética, Hospital JM Ramos Mejia
Accession: SCV001424331.1
First in ClinVar: Oct 23, 2020 Last updated: Oct 23, 2020 |
Sex: female
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Pathogenic
(Dec 02, 2021)
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criteria provided, single submitter
Method: clinical testing
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Neurodegeneration with brain iron accumulation 5
Affected status: yes
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV002061746.2
First in ClinVar: Jan 22, 2022 Last updated: Feb 11, 2022 |
Comment:
PVS1, PS2, PS4, PM2
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Pathogenic
(Mar 16, 2022)
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criteria provided, single submitter
Method: research
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Neurodegeneration with brain iron accumulation 5
(X-linked dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Laboratory of Human Genetics, Universidade de São Paulo
Accession: SCV002506518.1
First in ClinVar: May 07, 2022 Last updated: May 07, 2022 |
Comment:
This variant meets our criteria to be classified as pathogenic based upon segregation studies, absence from controls, and in-silico evaluation of pathogenicity. This variant was … (more)
This variant meets our criteria to be classified as pathogenic based upon segregation studies, absence from controls, and in-silico evaluation of pathogenicity. This variant was disclosed in a girl presenting with intellectual disability and X-chromosome inactivation skewing. (less)
Clinical Features:
Intellectual disability (present)
Age: 0-9 years
Sex: female
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Pathogenic
(Sep 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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X-linked cerebral-cerebellar-coloboma syndrome syndrome
(X-linked inheritance)
Affected status: yes
Allele origin:
de novo
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Baylor Genetics
Accession: SCV000807258.2
First in ClinVar: Sep 17, 2018 Last updated: Dec 11, 2022 |
Comment:
This variant was previously reported as pathogenic and was found once in our laboratory de novo in a 3-year-old female with infantile spasms, global developmental … (more)
This variant was previously reported as pathogenic and was found once in our laboratory de novo in a 3-year-old female with infantile spasms, global developmental delay, and normal brain MRI. (less)
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Pathogenic
(Apr 20, 2023)
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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: SCV000491043.4
First in ClinVar: Jan 09, 2017 Last updated: May 06, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23176820, 29981852, 25744623, 23687123, 26609730, 30369941, 25326635, 29445477, 27030146, 33084218, 33843443, 34077496) (less)
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Pathogenic
(Apr 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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Neurodegeneration with brain iron accumulation 5
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001234057.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This premature translational stop signal has been observed in individual(s) with neurodegeneration with brain iron accumulation (NBIA), epileptic spasms and developmental delay, and West syndrome … (more)
This premature translational stop signal has been observed in individual(s) with neurodegeneration with brain iron accumulation (NBIA), epileptic spasms and developmental delay, and West syndrome (PMID: 23176820, 25744623, 26609730, 27030146). In at least one individual the variant was observed to be de novo. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 212592). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg134*) in the WDR45 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WDR45 are known to be pathogenic (PMID: 23176820, 24368176, 24621584, 25744623, 26790960, 27030146, 27652284, 28554332). (less)
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Pathogenic
(Oct 01, 2019)
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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: SCV001247584.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Feb 09, 2016)
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no assertion criteria provided
Method: research
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Neurodegeneration with brain iron accumulation 5
Affected status: yes
Allele origin:
germline
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Division of Human Genetics, Children's Hospital of Philadelphia
Study: CSER-PediSeq
Accession: SCV000536742.1 First in ClinVar: Apr 23, 2017 Last updated: Apr 23, 2017 |
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Germline Functional Evidence
Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for this variant. |
Submitter
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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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Unknown function
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Consultorio y Laboratorio de Neurogenética, Hospital JM Ramos Mejia
Accession: SCV001424331.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Genomic diagnosis for children with intellectual disability and/or developmental delay. | Bowling KM | Genome medicine | 2017 | PMID: 28554332 |
Targeted sequencing of 351 candidate genes for epileptic encephalopathy in a large cohort of patients. | de Kovel CG | Molecular genetics & genomic medicine | 2016 | PMID: 27652284 |
WDR45 mutations in three male patients with West syndrome. | Nakashima M | Journal of human genetics | 2016 | PMID: 27030146 |
WDR45 mutations in Rett (-like) syndrome and developmental delay: Case report and an appraisal of the literature. | Hoffjan S | Molecular and cellular probes | 2016 | PMID: 26790960 |
Epileptic spasms: a previously unreported manifestation of WDR45 gene mutation. | Xixis KI | Epileptic disorders : international epilepsy journal with videotape | 2015 | PMID: 26609730 |
High frequency of beta-propeller protein-associated neurodegeneration (BPAN) among patients with intellectual disability and young-onset parkinsonism. | Nishioka K | Neurobiology of aging | 2015 | PMID: 25744623 |
De novo WDR45 mutation in a patient showing clinically Rett syndrome with childhood iron deposition in brain. | Ohba C | Journal of human genetics | 2014 | PMID: 24621584 |
Beta-propeller protein-associated neurodegeneration (BPAN), a rare form of NBIA: novel mutations and neuropsychiatric phenotype in three adult patients. | Verhoeven WM | Parkinsonism & related disorders | 2014 | PMID: 24368176 |
Exome sequencing reveals de novo WDR45 mutations causing a phenotypically distinct, X-linked dominant form of NBIA. | Haack TB | American journal of human genetics | 2012 | PMID: 23176820 |
Text-mined citations for rs797046101 ...
HelpRecord last updated Apr 15, 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.