VCV000620358.42 - ClinVar

NM_001029896.2(WDR45):c.52C>T (p.Gln18Ter)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic/Likely pathogenic
Pathogenic (2); Likely pathogenic (1)

3 out of 3 submissions contributed to this classification

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001029896.2(WDR45):c.52C>T (p.Gln18Ter)

Variation ID: 620358 Accession: VCV000620358.42

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xp11.23 X: 49078044 (GRCh38) [ NCBI UCSC ] X: 48935703 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Mar 19, 2019	Jun 20, 2026	Oct 21, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NM_001029896.2:c.52C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001025067.1:p.Gln18Ter	nonsense
NM_007075.4:c.52C>T	NP_009006.2:p.Gln18Ter	nonsense
NC_000023.11:g.49078044G>A
NC_000023.10:g.48935703G>A
NG_033004.2:g.28127C>T

... more HGVS ... less HGVS

Protein change

Q18*

Other names

Canonical SPDI

NC_000023.11:49078043:G:A

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA412949480 dbSNP: rs1569523562 VarSome

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
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help 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 Help 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.
WDR45		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	476	792
LOC126863256	-	-	-	GRCh38 GRCh38	-	226

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 Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Oct 21, 2019	RCV000760729.36
Neurodegeneration with brain iron accumulation 5	Likely pathogenic (1)	criteria provided, single submitter	Feb 3, 2019	RCV001194319.2

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.	Expand all rows Collapse all rows 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.
Likely pathogenic (Feb 03, 2019) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Neurodegeneration with brain iron accumulation 5	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV001363754.1 First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020	Comment: show Variant summary: WDR45 c.52C>T (p.Gln18X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by other laboratories in ClinVar (eg. c.400C>T (p.Arg134X) and c.210_213dup (p.Pro72Terfs)). The variant was absent in 200371 control chromosomes (gnomAD). To our knowledge, no occurrence of c.52C>T in individuals affected with Neurodegeneration with brain iron accumulation 5 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Oct 21, 2019) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000890621.2 First in ClinVar: Mar 19, 2019 Last updated: Sep 26, 2021	Comment: show 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 (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32387008) (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Jun 01, 2019) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV001247588.38 First in ClinVar: May 12, 2020 Last updated: Jun 20, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Comment:

Variant summary: WDR45 c.52C>T (p.Gln18X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by other laboratories in ClinVar (eg. c.400C>T (p.Arg134X) and c.210_213dup (p.Pro72Terfs)). The variant was absent in 200371 control chromosomes (gnomAD). To our knowledge, no occurrence of c.52C>T in individuals affected with Neurodegeneration with brain iron accumulation 5 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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 observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32387008)

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs1569523562 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 20, 2026