NM_001163809.2(WDR81):c.1358dup (p.Tyr453Ter) AND Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 13, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002266320.1

Allele description [Variation Report for NM_001163809.2(WDR81):c.1358dup (p.Tyr453Ter)]

NM_001163809.2(WDR81):c.1358dup (p.Tyr453Ter)

Gene:

WDR81:WD repeat domain 81 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

17p13.3

Genomic location:

Preferred name:

NM_001163809.2(WDR81):c.1358dup (p.Tyr453Ter)

HGVS:

NC_000017.11:g.1726317dup
NG_032811.1:g.14795dup
NM_001163673.2:c.59-4063dup
NM_001163809.2:c.1358dupMANE SELECT
NM_001163811.2:c.-15+1531dup
NM_152348.4:c.-123-1673dup
NP_001157281.1:p.Tyr453Ter
NC_000017.10:g.1629611dup
NM_001163809.1:c.1358dupA

Protein change:

Y453*

Links:

dbSNP: rs1194329020

NCBI 1000 Genomes Browser:

rs1194329020

Molecular consequence:

NM_001163673.2:c.59-4063dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001163811.2:c.-15+1531dup - intron variant - [Sequence Ontology: SO:0001627]
NM_152348.4:c.-123-1673dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001163809.2:c.1358dup - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2 (CAMRQ2)
Synonyms:: CEREBELLAR ATAXIA AND MENTAL RETARDATION WITH OR WITHOUT QUADRUPEDAL LOCOMOTION 2; Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2; CEREBELLAR ATAXIA, IMPAIRED INTELLECTUAL DEVELOPMENT, AND DYSEQUILIBRIUM SYNDROME 2
Identifiers:: MONDO: MONDO:0012430; MedGen: C2750234; Orphanet: 1766; OMIM: 610185

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002548152	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (May 13, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002548152

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(May 13, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

WDR81 mutations cause extreme microcephaly and impair mitotic progression in human fibroblasts and Drosophila neural stem cells.

Cavallin M, Rujano MA, Bednarek N, Medina-Cano D, Bernabe Gelot A, Drunat S, Maillard C, Garfa-Traore M, Bole C, Nitschké P, Beneteau C, Besnard T, Cogné B, Eveillard M, Kuster A, Poirier K, Verloes A, Martinovic J, Bidat L, Rio M, Lyonnet S, Reilly ML, et al.

Brain. 2017 Oct 1;140(10):2597-2609. doi: 10.1093/brain/awx218.

PubMed [citation]

PMID:: 28969387

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002548152.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Variant summary: WDR81 c.1358dupA (p.Tyr453X) 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 our laboratory. The variant allele was found at a frequency of 1.3e-05 in 152652 control chromosomes. c.1358dupA has been reported in the literature in individuals affected with Cerebellar Ataxia, Intellectual Disability, And Dysequilibrium Syndrome 2. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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