NM_001029896.2(WDR45):c.1027del (p.Cys343fs) AND Neurodegeneration with brain iron accumulation 5

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 21, 2019
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:: RCV001054071.6

Allele description [Variation Report for NM_001029896.2(WDR45):c.1027del (p.Cys343fs)]

NM_001029896.2(WDR45):c.1027del (p.Cys343fs)

Gene:

WDR45:WD repeat domain 45 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xp11.23

Genomic location:

Preferred name:

NM_001029896.2(WDR45):c.1027del (p.Cys343fs)

HGVS:

NC_000023.11:g.49074859del
NG_033004.2:g.31312del
NM_001029896.2:c.1027delMANE SELECT
NM_007075.4:c.1030del
NP_001025067.1:p.Cys343fs
NP_009006.2:p.Cys344fs
NP_009006.2:p.Cys344fs
NC_000023.10:g.48932518del
NM_007075.3:c.1030del

Protein change:

C343fs

Links:

dbSNP: rs2065026878

NCBI 1000 Genomes Browser:

rs2065026878

Molecular consequence:

NM_001029896.2:c.1027del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_007075.4:c.1030del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Neurodegeneration with brain iron accumulation 5 (NBIA5)
Synonyms:: STATIC ENCEPHALOPATHY OF CHILDHOOD WITH NEURODEGENERATION IN ADULTHOOD; Beta-propeller protein-associated neurodegeneration
Identifiers:: MONDO: MONDO:0010476; MedGen: C3550973; Orphanet: 329284; OMIM: 300894

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001218364	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 21, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24368176, 24896178, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001218364

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 21, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Beta-propeller protein-associated neurodegeneration (BPAN), a rare form of NBIA: novel mutations and neuropsychiatric phenotype in three adult patients.

Verhoeven WM, Egger JI, Koolen DA, Yntema H, Olgiati S, Breedveld GJ, Bonifati V, van de Warrenburg BP.

Parkinsonism Relat Disord. 2014 Mar;20(3):332-6. doi: 10.1016/j.parkreldis.2013.11.019. Epub 2013 Dec 10.

PubMed [citation]

PMID:: 24368176

Genome sequencing identifies major causes of severe intellectual disability.

Gilissen C, Hehir-Kwa JY, Thung DT, van de Vorst M, van Bon BW, Willemsen MH, Kwint M, Janssen IM, Hoischen A, Schenck A, Leach R, Klein R, Tearle R, Bo T, Pfundt R, Yntema HG, de Vries BB, Kleefstra T, Brunner HG, Vissers LE, Veltman JA.

Nature. 2014 Jul 17;511(7509):344-7. doi: 10.1038/nature13394. Epub 2014 Jun 4.

PubMed [citation]

PMID:: 24896178

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001218364.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change results in a frameshift in the WDR45 gene (p.Cys344Alafs*67). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 18 amino acids of the WDR45 protein and extend the protein by an additional 48 amino acids. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in individuals affected with WDR45-related disease (PMID: 24368176, 24896178). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been 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: Feb 20, 2024

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