NM_000377.3(WAS):c.1085del (p.Pro362fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 4, 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:: RCV001950664.6

Allele description [Variation Report for NM_000377.3(WAS):c.1085del (p.Pro362fs)]

NM_000377.3(WAS):c.1085del (p.Pro362fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

Xp11.23

Genomic location:

Preferred name:

NM_000377.3(WAS):c.1085del (p.Pro362fs)

HGVS:

NC_000023.11:g.48688813del
NG_007877.1:g.10017del
NM_000377.3:c.1085delMANE SELECT
NP_000368.1:p.Pro362fs
LRG_125:g.10017del
NC_000023.10:g.48547198del
NC_000023.10:g.48547202del

Protein change:

P362fs

Links:

dbSNP: rs2147266474

NCBI 1000 Genomes Browser:

rs2147266474

Molecular consequence:

NM_000377.3:c.1085del - 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
SCV002217987	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 4, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 8595430, 22426750, 15284122, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002217987

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 4, 2023)

germline

clinical testing

PubMed (4)
[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

Scanning of the Wiskott-Aldrich syndrome (WAS) gene: identification of 18 novel alterations including a possible mutation hotspot at Arg86 resulting in thrombocytopenia, a mild WAS phenotype.

Kwan SP, Hagemann TL, Blaese RM, Knutsen A, Rosen FS.

Hum Mol Genet. 1995 Oct;4(10):1995-8. No abstract available.

PubMed [citation]

PMID:: 8595430

Outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome.

Shin CR, Kim MO, Li D, Bleesing JJ, Harris R, Mehta P, Jodele S, Jordan MB, Marsh RA, Davies SM, Filipovich AH.

Bone Marrow Transplant. 2012 Nov;47(11):1428-35. doi: 10.1038/bmt.2012.31. Epub 2012 Mar 19.

PubMed [citation]

PMID:: 22426750

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002217987.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1441543). This variant is also known as c.1119del. This premature translational stop signal has been observed in individual(s) with Wiskott-Aldrich syndrome (PMID: 8595430, 22426750). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro362Glnfs*83) in the WAS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WAS are known to be pathogenic (PMID: 15284122).

#	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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