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]

Link to SEPIO compliant JSON-LD document

CA8622881

Gene: ITGB3

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 21f99660-8570-49a7-90aa-7287d412e9b8

HGVS expressions

NM_000212.3:c.166-14C>A

NC_000017.11:g.47283340C>A

CM000679.2:g.47283340C>A

NC_000017.10:g.45360706C>A

CM000679.1:g.45360706C>A

NC_000017.9:g.42715705C>A

NG_008332.2:g.34499C>A

ENST00000559488.7:c.166-14C>A

ENST00000559488.5:c.166-14C>A

ENST00000560629.1:n.131-14C>A

ENST00000571680.1:c.166-14C>A

NM_000212.2:c.166-14C>A

Uncertain Significance

PM3_Supporting PM2_Supporting BP7 PP4_Moderate

Evidence Links 0

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

The ITGB3 intronic variant NM_000212.3:c.166-14C>A is not predicted by in silico tools to have an impact on splicing. This variant has been observed in homozygosity in one individual with a phenotype specific for Glanzmann's thrombasthenia (GT) (GT03, PMID: 16463284). This variant is rare in population databases (1/30542 alleles in the South Asian population in gnomAD v2.1.1 and not observed in gnomAD v3.1.1). 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: PP4_Moderate, PM2_Supporting, PM3_Supporting, and BP7.

PM3_Supporting

This variant was reported in homozygosity in one individual (GT03 in PMID: 16463284), sufficient to apply PM3_Supporting.

PM2_Supporting

This variant is rare in population databases. It was observed in 1/30542 alleles in the South Asian population in gnomAD v2.1.1 and not observed in gnomAD v3.1.1. The frequency of this variant is below the 1/10000 allele threshold required to apply PM2_Supporting.

BP7

The intronic variant is not predicted to impact the splice consensus sequence according to varSEAK, MaxEntScan, and SpliceAI. The nucleotide is not highly conserved (phyloP score -0.57).

PP4_Moderate

All requirements for PP4_Moderate are met (GT03 in PMID: 16463284): history of bleeding and impaired aggregation to at least two agonists, but normal or only mildly reduced agglutination with ristocetin.

Approved on: 2021-07-14

Published on: 2021-12-23

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