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NM_000212.3(ITGB3):c.225_226del (p.Ala76fs) AND Glanzmann thrombasthenia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 9, 2021
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:
RCV001803406.2

Allele description [Variation Report for NM_000212.3(ITGB3):c.225_226del (p.Ala76fs)]

NM_000212.3(ITGB3):c.225_226del (p.Ala76fs)

Gene:
ITGB3:integrin subunit beta 3 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
17q21.32
Genomic location:
Preferred name:
NM_000212.3(ITGB3):c.225_226del (p.Ala76fs)
Other names:
NM_000212.3:c.225_226del
HGVS:
  • NC_000017.11:g.47283411TG[1]
  • NG_008332.2:g.34570TG[1]
  • NM_000212.3:c.225_226delMANE SELECT
  • NP_000203.2:p.Ala76fs
  • LRG_481:g.34570TG[1]
  • NC_000017.10:g.45360777TG[1]
  • NC_000017.10:g.45360777_45360778del
  • NC_000017.11:g.47283413_47283414del
Protein change:
A76fs
Links:
dbSNP: rs1438135616
NCBI 1000 Genomes Browser:
rs1438135616
Molecular consequence:
  • NM_000212.3:c.225_226del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV002047556ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen Platelet ACMG Specifications v2)		Pathogenic
(Nov 9, 2021) 		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, SCV002047556.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

NM_000212.3(ITGB3):c.225_226del (p.Ala76ProfsTer10) in exon 3 of ITGB3 is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 3/15 and is predicted to lead to nonsense mediated decay (PVS1). GT7 of PMID: 32237906 displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). Additionally, β3 surface expression was reduced to 0.3%, as measured by flow cytometry. GT7 (PMID: 32237906) is compound heterozygous for c.225_226del and Arg242Ter (classified Pathogenic by the PD-VCEP; PM3_supporting). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0001087 (2/18394 alleles) in the East Asian population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1, PP4_moderate, PM2_supporting, PM3_supporting. (VCEP specifications version 2; date of approval 11/04/2021)

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

Last Updated: Sep 29, 2024