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_000212.3:c.877C>T

CA400025022

953048 (ClinVar)

Gene: ITGB3 (HGNC:3690)

Condition: Glanzmann thrombasthenia (MONDO:0100326)

Inheritance Mode: Autosomal recessive inheritance

UUID: 009e5e3b-aeb7-448e-b62e-d46e1bab6c17

Approved on: 2026-09-03

Published on: 2026-09-04

HGVS expressions

NM_000212.3:c.877C>T

NC_000017.11:g.47287169C>T

CM000679.2:g.47287169C>T

NC_000017.10:g.45364535C>T

CM000679.1:g.45364535C>T

NC_000017.9:g.42719534C>T

NG_008332.2:g.38328C>T

ENST00000696963.1:c.877C>T

ENST00000559488.7:c.877C>T

ENST00000559488.5:c.877C>T

ENST00000560629.1:c.842C>T

ENST00000571680.1:c.877C>T

NM_000212.2:c.877C>T

Likely Pathogenic

PM2_Supporting PVS1

PP4 PM3

Evidence Links 0

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.877C>T variant results in premature termination of translation at Gln293 in exon 6/15. The resulting transcript is predicted to undergo NMD (PVS1). The highest population minor allele frequency in gnomAD v4.1 is 0.00001098 (1/91072 alleles) in the South Asian genetic ancestry group, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). The variant is reported in one compound heterozygous individual who does not meet criteria for PP4 (PMID: 30138987). 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, PVS1 (PD VCEP specifications version 2.1).

PM2_Supporting

The highest population minor allele frequency in gnomAD v4.1 is 0.00001098 (1/91072 alleles) in the South Asian genetic ancestry group, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting).

PVS1

The nonsense variant occurs in exon 6 of 15 and the resulting transcript is predicted to undergo NMD.

PP4

Patient 8 from PMID: 30138987 with hemorrhage, and <5% αIIbβ3 expression by flow cytometry. This patient does not meet criteria for PP4 due to insufficient aggregometry results (impaired aggregation with 1 agonist and normal with ristocetin).

PM3

Patient 8 in PMID: 30138987 is compound het individual with c.1260G>A (Thr420=) phase unknown, which has been classified Likely Pathogenic by the PD-VCEP. 0.25pt

Curation History

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