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.2T>C

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA400028186

Gene: ITGB3

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 825f0739-77f8-41fe-8852-2f5c8ddbbb9e

Approved on: 2023-04-06

Published on: 2023-04-07

HGVS expressions

NM_000212.3:c.2T>C

NC_000017.11:g.47253863T>C

CM000679.2:g.47253863T>C

NC_000017.10:g.45331229T>C

CM000679.1:g.45331229T>C

NC_000017.9:g.42686228T>C

NG_008332.2:g.5022T>C

ENST00000559488.7:c.2T>C

ENST00000559488.5:c.2T>C

ENST00000571680.1:c.2T>C

NM_000212.2:c.2T>C

Uncertain Significance

PVS1_Moderate PM3_Supporting PM2_Supporting

PP4

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

The NM_000212.3(ITGB3):c.2T>C (p.Met1Thr) may cause a truncated or absent protein by altering the start codon of the coding sequence and is predicted to lead to the omission of a critical region of the protein. At least one variant (c.31T>C; p.Trp11Arg) has been classified Pathogenic upstream of the next potential in-frame start codon at residue 48 (PVS1_Moderate). Patient 1, of PMID: 31029159, is reported to have a clinical diagnosis of GT and is homozygous for this variant (PM3_supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1_moderate, PM2_supporting, PM3_supporting (VCEP specifications version 2.1).

PVS1_Moderate

PM3_Supporting

Patient 1 is homozygous (by consanguinity) for this variant 0.5pt (PM3_supporting).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

PP4

Patient 1 of PMID: 31029159 is reported to have a clinical diagnosis of GT with a bleeding time of 20min, however insufficient information is provided including a lack of platelet aggregation results (PP4_NotMet).

Curation History

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