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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:
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:
RCV001290494.2

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

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

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.1021G>A (p.Ala341Thr)
HGVS:
  • 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:
A341T
Links:
dbSNP: rs2048616842
NCBI 1000 Genomes Browser:
rs2048616842
Molecular consequence:
  • NM_000419.5:c.1021G>A - missense variant - [Sequence Ontology: SO:0001583]

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

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

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

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

Description

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).

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

Last Updated: Jun 29, 2024