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NM_000419.5(ITGA2B):c.1021G>A (p.Ala341Thr) AND Glanzmann thrombasthenia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 7, 2024
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:

Allele description [Variation Report for NM_000419.5(ITGA2B):c.1021G>A (p.Ala341Thr)]

NM_000419.5(ITGA2B):c.1021G>A (p.Ala341Thr)

ITGA2B:integrin subunit alpha 2b [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000419.5(ITGA2B):c.1021G>A (p.Ala341Thr)
  • NC_000017.11:g.44383682C>T
  • NG_008331.1:g.10824G>A
  • NM_000419.5:c.1021G>AMANE SELECT
  • NP_000410.2:p.Ala341Thr
  • LRG_479:g.10824G>A
  • NC_000017.10:g.42461050C>T
  • NM_000419.4:c.1021G>A
Protein change:
dbSNP: rs2048616842
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000419.5:c.1021G>A - missense variant - [Sequence Ontology: SO:0001583]


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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001478533ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen Platelet ACMG Specifications v2-1)
Likely Pathogenic
(Mar 7, 2024)

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen, SCV001478533.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided


The NM_000419.5:c.1021G>A variant in ITGA2B is a missense variant predicted to cause substitution of Alanine by Threonine at amino acid 341. At least one patient (Patient 5 in PMID:32089034) homozygous for this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). A second homozygous case has also been identified (Northern Blood Research Centre, Kolling Institute, at The University of Sydney; PM3). This variant occurs at a MAF of 0.000002737 (3/1096028 alleles) in the European (non-Finnish) population, which is below the <0.0001 threshold for PM2_supporting. The computational predictor REVEL gives a score of 0.737, which is above the ClinGen PD VCEP threshold of >0.7 and predicts a damaging effect on function (PP3). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PP4_moderate, PM3, PM2_supporting, PP3. (VCEP specifications version 2).

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

Last Updated: Jun 29, 2024