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NM_000419.5(ITGA2B):c.2267+1G>T AND Glanzmann thrombasthenia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 1, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV001225274.3

Allele description [Variation Report for NM_000419.5(ITGA2B):c.2267+1G>T]

NM_000419.5(ITGA2B):c.2267+1G>T

Gene:
ITGA2B:integrin subunit alpha 2b [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_000419.5(ITGA2B):c.2267+1G>T
HGVS:
  • NC_000017.11:g.44377008C>A
  • NG_008331.1:g.17498G>T
  • NM_000419.5:c.2267+1G>TMANE SELECT
  • LRG_479:g.17498G>T
  • NC_000017.10:g.42454376C>A
  • NM_000419.4:c.2267+1G>T
Links:
dbSNP: rs2048550327
NCBI 1000 Genomes Browser:
rs2048550327
Molecular consequence:
  • NM_000419.5:c.2267+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Glanzmann thrombasthenia
Synonyms:
PLATELET GLYCOPROTEIN IIb-IIIa DEFICIENCY; Thrombasthenia of Glanzmann and Naegeli; Glanzmann thrombasthenia type A; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0100326; MedGen: C0040015; Orphanet: 849; OMIM: PS273800

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001397541ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen Platelet ACMG Specifications v2-1)		Pathogenic
(Dec 1, 2022) 		germlinecuration

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

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Clinical and molecular insights into Glanzmann's thrombasthenia in China.

Zhou L, Jiang M, Shen H, You T, Ding Z, Cui Q, Ma Z, Yang F, Xie Z, Shi H, Su J, Cao L, Lin J, Yin J, Dai L, Wang H, Wang Z, Yu Z, Ruan C, Xia L.

Clin Genet. 2018 Aug;94(2):213-220. doi: 10.1111/cge.13366. Epub 2018 May 22.

PubMed [citation]
PMID:
29675921
PMCID:
PMC6041146

Details of each submission

From ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen, SCV001397541.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

NM_000419.4:c.2267+1G>T is a canonical splice site variant that alters the donor site in intron 22. This is expected to result in aberrant splicing with skipping of exon 22 resulting in a frameshift with a premature stop codon in exon 24 which would lead to NMD (PVS1). It is absent from population databases (PM2_supporting). The variant is reported in 1 compound heterozygous individual with the Gln778Pro pathogenic variant in trans (PMID: 29675921; PM3_supporting). This patient has a phenotype highly specific to GT, including mucocutaneous bleeding, impaired aggregation with all agonists except ristocetin, and reduced surface expression of aIIbß3 measured by flow cytometry (PP4_strong). In summary, this variant is classified as pathogenic. GT-specific criteria applied: PVS1, PM2_Supporting, PM3_Supporting, and PP4_Strong.

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

Last Updated: Aug 13, 2023