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.166-14C>A

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA8622881

1330326 (ClinVar)

Gene: ITGB3

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

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

Approved on: 2024-08-20

Published on: 2024-08-20

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

ENST00000696963.1:c.166-14C>A

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

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

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

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

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

Uncertain Significance

PP4_Moderate PM3_Supporting PM2_Supporting BP7

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 ITGB3 intronic variant NM_000212.3:c.166-14C>A is not predicted by in silico tools to have an impact on splicing and is not highly conserved (BP7). This variant has been observed in homozygosity (PM3_supporting) in one individual with a phenotype specific for Glanzmann's thrombasthenia (GT) (GT03, PMID: 16463284). 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. This variant is rare in population databases (1/91018 alleles in the South Asian population in gnomAD v4.1.0; PM2_Supporting). 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.

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.

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 1/91018 alleles in the South Asian population in gnomAD v4.1.0. 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).

Curation History

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