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NM_000212.3(ITGB3):c.655G>A (p.Val219Met) AND Glanzmann thrombasthenia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 5, 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:
RCV003222557.3

Allele description [Variation Report for NM_000212.3(ITGB3):c.655G>A (p.Val219Met)]

NM_000212.3(ITGB3):c.655G>A (p.Val219Met)

Genes:
LOC130061043:ATAC-STARR-seq lymphoblastoid active region 12307 [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.655G>A (p.Val219Met)
Other names:
NM_000212.3:c.655G>A
HGVS:
  • NC_000017.11:g.47286300G>A
  • NG_008332.2:g.37459G>A
  • NM_000212.3:c.655G>AMANE SELECT
  • NP_000203.2:p.Val219Met
  • NP_000203.2:p.Val219Met
  • LRG_481t1:c.655G>A
  • LRG_481:g.37459G>A
  • LRG_481p1:p.Val219Met
  • NC_000017.10:g.45363666G>A
  • NC_000017.10:g.45363666G>A
  • NM_000212.2:c.655G>A
Protein change:
V219M
Molecular consequence:
  • NM_000212.3:c.655G>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
SCV003915971ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen Platelet ACMG Specifications v2-1)		Likely Pathogenic
(Sep 5, 2024) 		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, SCV003915971.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000212.3(ITGB3):c.655G>A (p.Val219Met) missense variant has been reported in at least one patient (Patient GTa, PMID:11722423) who displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). GTa is compound heterozygous for this variant and pathogenic variant c.602del (PM3). The highest population minor allele frequency in gnomAD v4.1 is 0.00001098 (1/91078 alleles) in the South Asian population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). The computational predictor REVEL gives a score of 0.874, 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: PM2_supporting, PM3, PP4_moderate, and PP3.

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

Last Updated: Oct 13, 2024