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NM_000212.3(ITGB3):c.740G>A (p.Gly247Asp) AND Glanzmann thrombasthenia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 20, 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:
RCV001580231.3

Allele description [Variation Report for NM_000212.3(ITGB3):c.740G>A (p.Gly247Asp)]

NM_000212.3(ITGB3):c.740G>A (p.Gly247Asp)

Gene:
ITGB3:integrin subunit beta 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.32
Genomic location:
Preferred name:
NM_000212.3(ITGB3):c.740G>A (p.Gly247Asp)
Other names:
G221D
HGVS:
  • NC_000017.11:g.47286385G>A
  • NG_008332.2:g.37544G>A
  • NM_000212.3:c.740G>AMANE SELECT
  • NP_000203.2:p.Gly247Asp
  • LRG_481:g.37544G>A
  • NC_000017.10:g.45363751G>A
  • NM_000212.2(ITGB3):c.740G>A
  • P05106:p.Gly247Asp
Protein change:
G247D; GLY221ASP
Links:
UniProtKB: P05106#VAR_069922; OMIM: 173470.0017; dbSNP: rs79560904
NCBI 1000 Genomes Browser:
rs79560904
Molecular consequence:
  • NM_000212.3:c.740G>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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001809868ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen Platelet ACMG Specifications v2-1)		Uncertain Significance
(Aug 20, 2024) 		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

AlphaIIbbeta3 integrin: new allelic variants in Glanzmann thrombasthenia, effects on ITGA2B and ITGB3 mRNA splicing, expression, and structure-function.

Jallu V, Dusseaux M, Panzer S, Torchet MF, Hezard N, Goudemand J, de Brevern AG, Kaplan C.

Hum Mutat. 2010 Mar;31(3):237-46. doi: 10.1002/humu.21179.

PubMed [citation]
PMID:
20020534

Details of each submission

From ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen, SCV001809868.2

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

Description

The ITGB3 missense variant NM_000212.3:c.740G>A replaces the glycine residue with an aspartate residue (p.Gly247Asp) and is absent from control population databases, including gonmADv4.1.0 (PM2_supporting). The variant is predicted by in silico tools to be damaging to protein function (REVEL score for this variant is 0.963; PP3). The functional impact has been assessed by flow cytometric detection of αIIb, β3, and αIIbβ3 positive cells following transient transfection of ITGB3 cDNA carrying this variant, showing a reduction in the number of positive cells (estimated to be ~7-19% compared to wild type; PMID: 20020534; PS3_supporting). This variant has been observed in heterozygosity in an individual suspected to have Glanzmann's thrombasthenia (GT) (CabGT-24 in PMID: 20020534), however sufficient information to confirm if the individual's phenotype is specific for GT was not provided and the second ITGB3 variant identified in the individual is of uncertain significance and unknown phase. In summary, this variant is of uncertain significance and lacks sufficient evidence to be classified as pathogenic or benign for GT. GT-specific criteria applied: PS3_supporting, PM2_supporting, PP3.

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

Last Updated: Oct 13, 2024