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NM_000419.5(ITGA2B):c.3099A>T (p.Glu1033Asp) AND Glanzmann thrombasthenia

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
May 2, 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:
RCV000852108.3

Allele description [Variation Report for NM_000419.5(ITGA2B):c.3099A>T (p.Glu1033Asp)]

NM_000419.5(ITGA2B):c.3099A>T (p.Glu1033Asp)

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.3099A>T (p.Glu1033Asp)
HGVS:
  • NC_000017.11:g.44372385T>A
  • NG_008331.1:g.22121A>T
  • NM_000419.4:c.3099A>T
  • NM_000419.5:c.3099A>TMANE SELECT
  • NP_000410.2:p.Glu1033Asp
  • LRG_479t1:c.3099A>T
  • LRG_479:g.22121A>T
  • NC_000017.10:g.42449753T>A
  • NM_000419.3:c.3099A>T
  • NM_000419.5(ITGA2B):c.3099A>TMANE SELECT
  • p.Glu1033Asp
Protein change:
E1033D
Links:
dbSNP: rs757116551
NCBI 1000 Genomes Browser:
rs757116551
Molecular consequence:
  • NM_000419.5:c.3099A>T - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000899666NIHR Bioresource Rare Diseases, University of Cambridge - ThromboGenomics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Feb 1, 2019) 		unknownresearch

PubMed (2)
[See all records that cite these PMIDs]

SCV001397476ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen Platelet ACMG Specifications v2-1)		Uncertain Significance
(May 2, 2024) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration
Europeanunknownyes1not providednot provided1not providedresearch

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders.

Downes K, Megy K, Duarte D, Vries M, Gebhart J, Hofer S, Shamardina O, Deevi SVV, Stephens J, Mapeta R, Tuna S, Al Hasso N, Besser MW, Cooper N, Daugherty L, Gleadall N, Greene D, Haimel M, Martin H, Papadia S, Revel-Vilk S, Sivapalaratnam S, et al.

Blood. 2019 Dec 5;134(23):2082-2091. doi: 10.1182/blood.2018891192.

PubMed [citation]
PMID:
31064749
PMCID:
PMC6993014

Details of each submission

From NIHR Bioresource Rare Diseases, University of Cambridge - ThromboGenomics, SCV000899666.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1European1not providednot providedresearch PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyes1not providednot provided1not providednot providednot provided

From ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen, SCV001397476.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The missense variant c.3099A>T (p.Glu1033Asp) has been reported heterozygous in one patient (PMID: 31064749) however a second variant was not identified. Communication with the authors confirmed the patient had decreased platelet glycoprotein IIb-IIIa, abnormal bleeding, and impaired platelet aggregation with ADP, epinephrine, arachidonic acid, and collagen. The highest population minor allele frequency in gnomAD v4.0.0 is 0.00003334 (2/59980 alleles) in the Admixed American population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). Computational predictors agree that this variant does not have a deleterious effect (REVEL score of 0.193; BP4). In summary, this variant meets criteria to be classified as uncertain significance for GT. GT-specific criteria applied: PM2_supporting, BP4.

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

Last Updated: Oct 13, 2024