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NM_000419.5(ITGA2B):c.3077G>A (p.Arg1026Gln) AND Glanzmann thrombasthenia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 7, 2023
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:
RCV001225267.4

Allele description [Variation Report for NM_000419.5(ITGA2B):c.3077G>A (p.Arg1026Gln)]

NM_000419.5(ITGA2B):c.3077G>A (p.Arg1026Gln)

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.3077G>A (p.Arg1026Gln)
Other names:
R995Q
HGVS:
  • NC_000017.11:g.44372407C>T
  • NG_008331.1:g.22099G>A
  • NM_000419.5:c.3077G>AMANE SELECT
  • NP_000410.2:p.Arg1026Gln
  • LRG_479t1:c.3077G>A
  • LRG_479:g.22099G>A
  • NC_000017.10:g.42449775C>T
  • NM_000419.3:c.3077G>A
  • NM_000419.4:c.3077G>A
  • NM_000419.5(ITGA2B):c.3077G>AMANE SELECT
  • P08514:p.Arg1026Gln
Protein change:
R1026Q; ARG995GLN
Links:
UniProtKB: P08514#VAR_030468; OMIM: 607759.0017; dbSNP: rs879255514
NCBI 1000 Genomes Browser:
rs879255514
Molecular consequence:
  • NM_000419.5:c.3077G>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

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001397533ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen Platelet ACMG Specifications v2-1)		Uncertain significance
(Sep 7, 2023) 		germlinecuration

Citation Link

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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, SCV001397533.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000419.5:c.3077G>A variant results in the Arg1026Gln missense change. It is absent in population databases, including gnomADv2.1.1 (PM2_supporting), and is predicted damaging by in silico tools (REVEL score of 0.904; PP3). One compound heterozygous individual with mild bleeding, thrombocytopenia and platelet anisotrpy is reported in the literature several times (PMID: 25728920) with confirmation of c.1440-13_1440-1del (classified Pathogenic by the PD VCEP; PM3) in trans. The variant results in reduced expression of the αIIbβ3 complex on platelet surface. The expressed αIIbβ3 was not constitutively active and were able to bind fibrinogen only upon activation by anti-LIBS antibody. In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_Supporting, PM3, PP3 (PD VCEP specifications version 2.1).

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

Last Updated: Jun 23, 2024