Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000212.2:c.115T>G

CA400031666

953043 (ClinVar)

Gene: ITGB3 (HGNC:3690)

Condition: Glanzmann thrombasthenia (MONDO:0100326)

Inheritance Mode: Autosomal recessive inheritance

UUID: 4c19257d-2ea0-4ff6-9dc1-e00dd5628fd8

Approved on: 2026-02-05

Published on: 2026-02-05

HGVS expressions

NM_000212.2:c.115T>G

NC_000017.11:g.47274454T>G

CM000679.2:g.47274454T>G

NC_000017.10:g.45351820T>G

CM000679.1:g.45351820T>G

NC_000017.9:g.42706819T>G

NG_008332.2:g.25613T>G

ENST00000696963.1:c.115T>G

ENST00000559488.7:c.115T>G

ENST00000559488.5:c.115T>G

ENST00000560629.1:c.80T>G

ENST00000571680.1:c.115T>G

NM_000212.3:c.115T>G

Likely Pathogenic

PM3_Supporting PS3_Moderate PM2_Supporting PP4_Moderate PP3

Evidence Links 1

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2.1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

The NM_000212.3(ITGB3):c.115T>G variant that results in the Cys39Gly amino acid change is reported in one homozygous individual in the literature (PMID: 16463284; PM3_supporting). Proband from PMID: 1646328 meets the criteria for PP4_Moderate; including mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin. It is absent in population database gnomADv4.1 (PM2_supporting) and is predicted damaging by in-silico tools (REVEL score of 0.939; PP3). Experimental evidence shows reduced surface expression of integrin αIIbβ3 PMID: 16463284; PS3_moderate). 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: PP4_moderate, PM2_supporting, PM3_supporting, PP3, PS3_moderate. (VCEP specifications version 2).

PM3_Supporting

One homozygous individual, GT11, from PMID: 16463284 meets criteria for PM3_Supporting.

Individual GT11 was predicted to be homozygous based on haplotype analysis and consanguinity status. PubMed:16463284

PS3_Moderate

Greatly reduced surface expression of integrin αIIbβ3 on BHK cells shown in PMID: 16463284 meets PS3_Moderate

Wildtype β3, Cys39Gly and artificial mutation, Cys13Ser, expression vectors were constructed and cotransfected into baby hamster kidney cells along with wildtype αIIb vector. FACS and Immunoblot analyses (Figure 5) detected trace amounts of αIIbβ3 protein. PubMed:16463284

PM2_Supporting

Variant is absent from gnomADv4.1 (PM2_supporting).

PP4_Moderate

Proband from PMID: 1646328 meets the criteria for PP4_Moderate; including mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin.

PP3

REVEL score of 0.939 meets PP3 criteria (threshold: >0.7)

Curation History

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