NM_000377.3(WAS):c.1040dup (p.Leu347fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 19, 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:: RCV003042620.3

Allele description [Variation Report for NM_000377.3(WAS):c.1040dup (p.Leu347fs)]

NM_000377.3(WAS):c.1040dup (p.Leu347fs)

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.1040dup (p.Leu347fs)

HGVS:

NC_000023.11:g.48688768dup
NG_007877.1:g.9972dup
NM_000377.3:c.1040dupMANE SELECT
NP_000368.1:p.Leu347Phefs
NP_000368.1:p.Leu347fs
LRG_125t1:c.1040dup
LRG_125:g.9972dup
LRG_125p1:p.Leu347Phefs
NC_000023.10:g.48547154_48547155insT
NC_000023.10:g.48547157dup
NM_000377.2:c.1040dup

Protein change:

L347fs

Molecular consequence:

NM_000377.3:c.1040dup - 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

Recent activity

Clear Turn Off Turn On

Pseudomonas furukawaii Cq-40 gene for 16S rRNA, partial sequence
Pseudomonas furukawaii Cq-40 gene for 16S rRNA, partial sequence
gi|2173284594|dbj|LC667809.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003332682	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 19, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 8528198, 11442475, 12727931, 24210885, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003332682

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 19, 2022)

germline

clinical testing

PubMed (5)
[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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003332682.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Leu347Phefs*148) in the WAS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 156 amino acid(s) of the WAS protein. 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 variant has not been reported in the literature in individuals affected with WAS-related conditions. This variant is not present in population databases (gnomAD no frequency).

#	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

ClinVar

Relating variation to medicine