NM_000377.3(WAS):c.1073dup (p.Pro359fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 17, 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:: RCV003783766.2

Allele description [Variation Report for NM_000377.3(WAS):c.1073dup (p.Pro359fs)]

NM_000377.3(WAS):c.1073dup (p.Pro359fs)

Gene:

WAS:WASP actin nucleation promoting factor [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

Xp11.23

Genomic location:

Preferred name:

NM_000377.3(WAS):c.1073dup (p.Pro359fs)

HGVS:

NC_000023.11:g.48688801dup
NG_007877.1:g.10005dup
NM_000377.3:c.1073dupMANE SELECT
NP_000368.1:p.Pro359Thrfs
NP_000368.1:p.Pro359fs
LRG_125t1:c.1073dup
LRG_125:g.10005dup
LRG_125p1:p.Pro359Thrfs
NC_000023.10:g.48547186_48547187insG
NC_000023.10:g.48547190dup
NM_000377.2:c.1073dup

Protein change:

P359fs

Molecular consequence:

NM_000377.3:c.1073dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: X-linked severe congenital neutropenia (SCNX)
Identifiers:: MONDO: MONDO:0010294; MedGen: C1845987; Orphanet: 86788; OMIM: 300299

Name:: Thrombocytopenia 1
Synonyms:: THROMBOCYTOPENIA, X-LINKED, 1; Thrombocytopenia, X-linked; X-linked thrombocytopenia with normal platelets
Identifiers:: MONDO: MONDO:0010743; MedGen: C1839163; Orphanet: 268322; OMIM: 313900

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004571396	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 17, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 8528198, 11442475, 12727931, 24210885, 21185603, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004571396

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 17, 2023)

germline

clinical testing

PubMed (6)
[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

Identification of WASP mutations in patients with Wiskott-Aldrich syndrome and isolated thrombocytopenia reveals allelic heterogeneity at the WAS locus.

Kolluri R, Shehabeldin A, Peacocke M, Lamhonwah AM, Teichert-Kuliszewska K, Weissman SM, Siminovitch KA.

Hum Mol Genet. 1995 Jul;4(7):1119-26.

PubMed [citation]

PMID:: 8528198

Protein assays for diagnosis of Wiskott-Aldrich syndrome and X-linked thrombocytopenia.

Qasim W, Gilmour KC, Heath S, Ashton E, Cranston T, Thomas A, Finn A, Davies EG, Thrasher AJ, Kinnon C, Jones A, Gaspar HB.

Br J Haematol. 2001 Jun;113(4):861-5.

PubMed [citation]

PMID:: 11442475

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004571396.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the WAS protein in which other variant(s) (p.Leu425Profs*70) have been determined to be pathogenic (PMID: 8528198, 11442475, 12727931, 24210885). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This premature translational stop signal has been observed in individual(s) with Wiskott-Aldrich syndrome (PMID: 21185603). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro359Thrfs*136) in the WAS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 144 amino acid(s) of the WAS protein.

#	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: Sep 29, 2024

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