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NM_000377.3(WAS):c.805A>T (p.Ser269Cys) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 21, 2021
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:
RCV001982034.5

Allele description [Variation Report for NM_000377.3(WAS):c.805A>T (p.Ser269Cys)]

NM_000377.3(WAS):c.805A>T (p.Ser269Cys)

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.805A>T (p.Ser269Cys)
HGVS:
  • NC_000023.11:g.48688327A>T
  • NG_007877.1:g.9531A>T
  • NM_000377.3:c.805A>TMANE SELECT
  • NP_000368.1:p.Ser269Cys
  • LRG_125:g.9531A>T
  • NC_000023.10:g.48546716A>T
Protein change:
S269C
Links:
dbSNP: rs2147265903
NCBI 1000 Genomes Browser:
rs2147265903
Molecular consequence:
  • NM_000377.3:c.805A>T - missense variant - [Sequence Ontology: SO:0001583]

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

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002212848Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 21, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002212848.2

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). This variant has been observed in individual(s) with clinical features of WAS-related conditions (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with cysteine at codon 269 of the WAS protein (p.Ser269Cys). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and cysteine.

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

Last Updated: Sep 29, 2024