NM_001029896.2(WDR45):c.2T>C (p.Met1Thr) AND Neurodegeneration with brain iron accumulation 5

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 18, 2021
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:
RCV002272799.3

Allele description [Variation Report for NM_001029896.2(WDR45):c.2T>C (p.Met1Thr)]

NM_001029896.2(WDR45):c.2T>C (p.Met1Thr)

Genes:
LOC126863256:BRD4-independent group 4 enhancer GRCh37_chrX:48934848-48936047 [Gene]
WDR45:WD repeat domain 45 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp11.23
Genomic location:
Preferred name:
NM_001029896.2(WDR45):c.2T>C (p.Met1Thr)
HGVS:
  • NC_000023.11:g.49078094A>G
  • NG_033004.2:g.28077T>C
  • NM_001029896.2:c.2T>CMANE SELECT
  • NM_007075.4:c.2T>C
  • NP_001025067.1:p.Met1Thr
  • NP_009006.2:p.Met1Thr
  • NC_000023.10:g.48935753A>G
  • NM_007075.3:c.2T>C
Protein change:
M1T
Links:
dbSNP: rs1569523565
NCBI 1000 Genomes Browser:
rs1569523565
Molecular consequence:
  • NM_001029896.2:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_007075.4:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001029896.2:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007075.4:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002557020Genetics and Molecular Pathology, SA Pathology

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(May 18, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Genetics and Molecular Pathology, SA Pathology, SCV002557020.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The WDR45 c.2T>C variant is a single nucleotide change which is predicted to result in loss of the start codon. The resultant protein is predicted to be comprised of only the final 76 residues out of 362, which is a loss of >10% (PVS_Strong). This variant is de novo in this individual (PS2). This variant has not been reported in dbSNP and is absent from population databases (PM2). This variant has not been reported in the ClinVar of HGMD disease databases, although a different change affecting the same nucleotide and resulting in the same start loss effect (c.2T>A) has been reported as pathogenic / likely pathogenic in ClinVar for neurodegeneration with brain iron accumulation 5 (ClinVar variation ID: 620005). The WDR45 c.2T>C variant is classified as PATHOGENIC (PM2, PS2, PVS1_Strong)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024