ClinVar Genomic variation as it relates to human health
NM_032856.5(WDR73):c.287G>A (p.Arg96Lys)
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_032856.5(WDR73):c.287G>A (p.Arg96Lys)
Variation ID: 208470 Accession: VCV000208470.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 15q25.2 15: 84648537 (GRCh38) [ NCBI UCSC ] 15: 85191768 (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 30, 2017 Jul 22, 2023 Dec 22, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_032856.5:c.287G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_116245.2:p.Arg96Lys missense NR_130944.2:n.830G>A non-coding transcript variant NR_130945.2:n.296G>A non-coding transcript variant NR_130946.2:n.303G>A non-coding transcript variant NC_000015.10:g.84648537C>T NC_000015.9:g.85191768C>T NG_042034.1:g.10807G>A - Protein change
- R96K
- Other names
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- Canonical SPDI
- NC_000015.10:84648536: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
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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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WDR73 | - | - |
GRCh38 GRCh38 GRCh37 |
193 | 247 |
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
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
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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/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Dec 22, 2021 | RCV000190493.15 | |
Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 23, 2020 | RCV000657966.3 | |
Likely pathogenic (1) |
no assertion criteria provided
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Nov 10, 2017 | RCV001849333.1 |
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
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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
(May 25, 2018)
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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: SCV000779737.2
First in ClinVar: Jul 09, 2018 Last updated: Jul 09, 2018 |
Comment:
The c.287G>A variant in the WDR73 gene has been reported previously in association with Galloway-Mowat syndrome, in affected individuals who were homozygous for the R96K … (more)
The c.287G>A variant in the WDR73 gene has been reported previously in association with Galloway-Mowat syndrome, in affected individuals who were homozygous for the R96K variant (Vodopiutz et al., 2015; Rosti et al., 2016). The c.287G>A variant is not observed in large population cohorts (Lek et al., 2016). In-silico splice models predict that c.287G>A may damage or destroy the canonical splice donor site in intron 4. However, in the absence of RNA/functional studies, the actual effect of the c.287G>A change in this individual is unknown. If c.287G>A does not alter splicing, it will result in the R96K missense change. The R96K variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret c.287G>A as a likely pathogenic variant. (less)
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Likely pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446480.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Optic atrophy (present) , Global developmental delay (present) , Septo-optic dysplasia sequence (present) , Sleep abnormality (present) , Constipation (present) , Microcephaly (present) , Hypotonia … (more)
Optic atrophy (present) , Global developmental delay (present) , Septo-optic dysplasia sequence (present) , Sleep abnormality (present) , Constipation (present) , Microcephaly (present) , Hypotonia (present) , Strabismus (present) , Nystagmus (present) (less)
Sex: female
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Likely pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Galloway-Mowat syndrome 1
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV002072970.1
First in ClinVar: Feb 04, 2022 Last updated: Feb 04, 2022 |
Comment:
The missense variant p.R96K in WDR73 (NM_032856.5) has been reported previously in affected individuals (Vodopiutz J et al; Rosti et al). It has been submitted … (more)
The missense variant p.R96K in WDR73 (NM_032856.5) has been reported previously in affected individuals (Vodopiutz J et al; Rosti et al). It has been submitted to ClinVar as Likely pathogenic/Pathogenic. The p.R96K variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. In silico tools predict the variant to be damaging and the residue is conserved across species. For these reasons, this variant has been classified as Likely Pathogenic (less)
Clinical Features:
Recurrent fever (present) , Failure to thrive (present) , Hypotonia (present) , Global developmental delay (present) , Cerebellar atrophy (present) , Oligohydramnios (present)
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Likely pathogenic
(Dec 22, 2021)
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criteria provided, single submitter
Method: clinical testing
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Galloway-Mowat syndrome 1
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002580531.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PS4_MOD, PM3, PM2_SUP, PP3
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Number of individuals with the variant: 1
Sex: female
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Pathogenic
(May 27, 2021)
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criteria provided, single submitter
Method: clinical testing
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Galloway-Mowat syndrome 1
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV002764949.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Number of individuals with the variant: 1
Clinical Features:
Hypotonia (present) , Hepatosplenomegaly (present) , Dyskinesia (present) , Microcephaly (present) , Cerebellar vermis hypoplasia (present) , Global developmental delay (present)
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Likely pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Galloway-Mowat syndrome 1
Affected status: yes
Allele origin:
unknown
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3billion
Accession: SCV004013669.1
First in ClinVar: Jul 22, 2023 Last updated: Jul 22, 2023 |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. In silico tools predict the variant to alter splicing and produce an abnormal transcript (SpliceAI: … (more)
The variant is not observed in the gnomAD v2.1.1 dataset. In silico tools predict the variant to alter splicing and produce an abnormal transcript (SpliceAI: 0.89). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000208470 / PMID: 26123727). The variant has been reported to co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated family (PMID: 27001912). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Generalized hypotonia (present) , Global developmental delay (present) , Microcephaly (present) , Short stature (present)
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Pathogenic
(Jun 29, 2015)
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no assertion criteria provided
Method: literature only
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GALLOWAY-MOWAT SYNDROME 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000245365.2
First in ClinVar: Sep 05, 2015 Last updated: Oct 30, 2017 |
Comment on evidence:
In a girl (patient 3), born of consanguineous Indian parents, with Galloway-Mowat syndrome-1 (GAMOS1; 251300), Vodopiutz et al. (2015) identified a homozygous c.287G-A transition (c.287G-A, … (more)
In a girl (patient 3), born of consanguineous Indian parents, with Galloway-Mowat syndrome-1 (GAMOS1; 251300), Vodopiutz et al. (2015) identified a homozygous c.287G-A transition (c.287G-A, NM_032856.3) in the WDR73 gene, resulting in an arg96-to-lys (R96K) substitution at a highly conserved residue in the N-terminal domain upstream of the WD40 repeats. Functional studies of the variant were not performed. The patient was 1 of 40 unrelated patients with a clinical diagnosis of GAMOS who underwent exome sequencing or Sanger sequencing of the WDR73 gene. (less)
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Pathogenic
(Mar 26, 2019)
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no assertion criteria provided
Method: clinical testing
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Galloway-Mowat syndrome 1
Affected status: yes
Allele origin:
germline
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Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare
Accession: SCV001192690.1
First in ClinVar: Mar 29, 2020 Last updated: Mar 29, 2020 |
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Likely pathogenic
(Nov 10, 2017)
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no assertion criteria provided
Method: literature only
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Nephrotic syndrome
Affected status: yes
Allele origin:
germline
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Yale Center for Mendelian Genomics, Yale University
Study: Yale Center for Mendelian Genomics
Accession: SCV002107062.1 First in ClinVar: Mar 28, 2022 Last updated: Mar 28, 2022 |
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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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Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome. | Warejko JK | Clinical journal of the American Society of Nephrology : CJASN | 2018 | PMID: 29127259 |
Extending the mutation spectrum for Galloway-Mowat syndrome to include homozygous missense mutations in the WDR73 gene. | Rosti RO | American journal of medical genetics. Part A | 2016 | PMID: 27001912 |
WDR73 Mutations Cause Infantile Neurodegeneration and Variable Glomerular Kidney Disease. | Vodopiutz J | Human mutation | 2015 | PMID: 26123727 |
Text-mined citations for rs797044995 ...
HelpRecord last updated Sep 01, 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.