Variant: NM_000419.5:c.1142C>T

CA399804396

1030779 (ClinVar)

Gene: ITGA2B

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

UUID: 04e75931-7e04-49cd-8465-eec168b78e7d

Approved on: 2024-02-20

Published on: 2024-02-20

HGVS expressions

NM_000419.5:c.1142C>T
NC_000017.11:g.44383561G>A
CM000679.2:g.44383561G>A
NC_000017.10:g.42460929G>A
CM000679.1:g.42460929G>A
NC_000017.9:g.39816455G>A
NG_008331.1:g.10945C>T
ENST00000262407.6:c.1142C>T
ENST00000648408.1:c.573C>T
ENST00000262407.5:c.1142C>T
ENST00000592226.5:n.382C>T
NM_000419.3:c.1142C>T
NM_000419.4:c.1142C>T
NM_000419.5(ITGA2B):c.1142C>T (p.Thr381Ile)

Uncertain Significance

• Met criteria codes: PM2_Supporting

• Not Met criteria codes: PP4 PP3 PM3 BP4

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

Evidence submitted by expert panel

Platelet Disorders VCEP

The ITGA2B missense variant NM_000419.5:c.1142C>T replaces the threonine residue with an isoleucine residue (p.Thr381Ile) and is absent from control population databases, including gonmADv4.0 (PM2_supporting). This variant has been observed in heterozygosity in an individual suspected to have Glanzmann's thrombasthenia (GT) (GT-71 in PMID: 30792900), however sufficient information to confirm if the individual's phenotype is specific for GT was not provided and a second ITGA2B variant was not identified. 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: PM2_supporting.

Met criteria codes

• PM2_Supporting: This is a rare variant not reported in control population databases, including gnomADv4.0 (PM2_supporting).

Not Met criteria codes

• PP4: This variant has been observed in an individual with a previous history of type III or variant Glanzmann thrombasthenia (GT-71 in PMID: 30792900), but sufficient phenotypic details and platelet aggregation information were not provided to apply PP4 at any strength level.
• PP3: The REVEL score for this variant is 0.361, below the VCEP-established threshold of ≥0.7 to apply PP3 and above the VCEP-established threshold of <0.25 to apply BP4. Additionally, splice predictors (SpliceAI and MaxEntScan) do not predict a damaging effect on splicing.
• PM3: This variant has been reported in heterozygosity in one proband (GT-71, PMID: 30792900), however a second ITGA2B variant was not identified.
• BP4: See explanation for PP3.