U.S. flag

An official website of the United States government

NM_000377.3(WAS):c.134C>T (p.Thr45Met) AND Wiskott-Aldrich syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 20, 2023
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:
RCV004760326.2

Allele description [Variation Report for NM_000377.3(WAS):c.134C>T (p.Thr45Met)]

NM_000377.3(WAS):c.134C>T (p.Thr45Met)

Gene:
WAS:WASP actin nucleation promoting factor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp11.23
Genomic location:
Preferred name:
NM_000377.3(WAS):c.134C>T (p.Thr45Met)
HGVS:
  • NC_000023.11:g.48684284C>T
  • NG_007877.1:g.5488C>T
  • NM_000377.3:c.134C>TMANE SELECT
  • NP_000368.1:p.Thr45Met
  • NP_000368.1:p.Thr45Met
  • LRG_125t1:c.134C>T
  • LRG_125:g.5488C>T
  • LRG_125p1:p.Thr45Met
  • NC_000023.10:g.48542673C>T
  • NM_000377.2:c.134C>T
  • P42768:p.Thr45Met
Protein change:
T45M; THR45MET
Links:
UniProtKB: P42768#VAR_008106; OMIM: 300392.0010; dbSNP: rs132630273
NCBI 1000 Genomes Browser:
rs132630273
Molecular consequence:
  • NM_000377.3:c.134C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Wiskott-Aldrich syndrome (WAS)
Synonyms:
Eczema thrombocytopenia immunodeficiency syndrome; Immunodeficiency 2; IMD 2; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010518; MedGen: C0043194; Orphanet: 906; OMIM: 301000

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV005373655Neuberg Centre For Genomic Medicine, NCGM
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(May 20, 2023)
germlineclinical testing

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

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 Neuberg Centre For Genomic Medicine, NCGM, SCV005373655.2

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

Description

The observed missense c.134C>T(p.Thr45Met) variant in WAS gene has been reported previously in X-linked state in individual(s) affected with Wiskott-Aldrich syndrome (Yue et al., 2022). This variant is absent in gnomAD Exomes. This variant has been reported to the ClinVar database as Pathogenic (multiple submitters). The amino acid Thr at position 45 is changed to a Met changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Thr45Met in WAS is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. Multiple lines of computational evidence (Polyphen - Damaging, SIFT - Damaging, and MutationTaster - Disease causing automatic) predict a damaging effect on protein structure and function for this variant. Experimental evidence indicated an impact on protein function and found that the variant partially impairs binding with WIP, an interaction proposed as causal to the disease (Rajmohan et al., 2009). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 24, 2024