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.428T>C

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA400021913

Gene: ITGB3

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: bd4d22f1-94e7-4730-8768-d8fd4cbc9b41

Approved on: 2024-03-07

Published on: 2024-03-08

HGVS expressions

NM_000212.3:c.428T>C

NC_000017.11:g.47284509T>C

CM000679.2:g.47284509T>C

NC_000017.10:g.45361875T>C

CM000679.1:g.45361875T>C

NC_000017.9:g.42716874T>C

NG_008332.2:g.35668T>C

ENST00000696963.1:c.428T>C

ENST00000559488.7:c.428T>C

ENST00000559488.5:c.428T>C

ENST00000560629.1:c.393T>C

ENST00000571680.1:c.428T>C

NM_000212.2:c.428T>C

Likely Pathogenic

PP3 PM3_Supporting PP4_Moderate PM2_Supporting PM5_Supporting

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.428T>C (p.Leu143Ser) missense variant is absent from gnomADv4.0.0 (PM2_supporting) and has a REVEL score of 0.973, above the >.0.7 threshold in support of a deleterious effect (PP3). Another missense variant NM_000212.3(ITGB3):c.428T>G (p.Leu143Trp) in the same codon has been classified as likely pathogenic for Glanzmann thrombasthenia by the ClinGen PD VCEP (PM5_supporting). It has been reported once, homozygous in Patient 15 of PMID: 36672149 has history of bleeding and impaired aggregation to at least two agonists, but normal agglutination with ristocetin (PM3_supporting; PP4_Moderate). In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Glanzmann thrombasthenia. GT-specific criteria applied: PM2_supporting, PP3, PM5_supporting, PM3_supporting, PP4_Moderate.

PP3

REVEL score of 0.973 is above the >.0.7 threshold in support of a deleterious effect.

PM3_Supporting

Patient 15 of PMID: 36672149 is homozygous (PM3_supporting).

PP4_Moderate

Patient 15 of PMID: 36672149 has history of bleeding and impaired aggregation to at least two agonists, but normal agglutination with ristocetin (PP4_Moderate).

PM2_Supporting

The variant is absent from gnomADv4.0.0 (PM2_supporting).

PM5_Supporting

Another missense variant NM_000212.3(ITGB3):c.428T>G (p.Leu143Trp) in the same codon has been classified as likely pathogenic for Glanzmann thrombasthenia by the ClinGen PD VCEP (PM5_supporting).

Curation History

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