NM_000377.3(WAS):c.778-6G>A AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 10, 2020
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:: RCV001387957.7

Allele description [Variation Report for NM_000377.3(WAS):c.778-6G>A]

NM_000377.3(WAS):c.778-6G>A

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.778-6G>A

HGVS:

NC_000023.11:g.48688294G>A
NG_007877.1:g.9498G>A
NM_000377.3:c.778-6G>AMANE SELECT
LRG_125t1:c.778-6G>A
LRG_125:g.9498G>A
NC_000023.10:g.48546683G>A
NM_000377.2:c.778-6G>A

Links:

dbSNP: rs1557007011

NCBI 1000 Genomes Browser:

rs1557007011

Molecular consequence:

NM_000377.3:c.778-6G>A - intron variant - [Sequence Ontology: SO:0001627]

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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NF-kB inactivation effect on T-ALL1 cell lines
NF-kB inactivation effect on T-ALL1 cell lines
Accession: GDS4213

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001588733	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 10, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20173115, 26368308, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001588733

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 10, 2020)

germline

clinical testing

PubMed (3)
[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

X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options.

Albert MH, Bittner TC, Nonoyama S, Notarangelo LD, Burns S, Imai K, Espanol T, Fasth A, Pellier I, Strauss G, Morio T, Gathmann B, Noordzij JG, Fillat C, Hoenig M, Nathrath M, Meindl A, Pagel P, Wintergerst U, Fischer A, Thrasher AJ, Belohradsky BH, et al.

Blood. 2010 Apr 22;115(16):3231-8. doi: 10.1182/blood-2009-09-239087. Epub 2010 Feb 19.

PubMed [citation]

PMID:: 20173115

Lentiviral-mediated gene therapy restores B cell tolerance in Wiskott-Aldrich syndrome patients.

Pala F, Morbach H, Castiello MC, Schickel JN, Scaramuzza S, Chamberlain N, Cassani B, Glauzy S, Romberg N, Candotti F, Aiuti A, Bosticardo M, Villa A, Meffre E.

J Clin Invest. 2015 Oct 1;125(10):3941-51. doi: 10.1172/JCI82249. Epub 2015 Sep 14.

PubMed [citation]

PMID:: 26368308
PMCID:: PMC4607131

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001588733.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with clinical features of Wiskott-Aldrich syndrome (PMID: 20173115, 26368308, Invitae, external communication). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 449116). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 8 of the WAS gene. It does not directly change the encoded amino acid sequence 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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