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_000419.5:c.2315C>G

CA8602740

2498355 (ClinVar)

Gene: ITGA2B (HGNC:3674)

Condition: Glanzmann thrombasthenia (MONDO:0100326)

Inheritance Mode: Autosomal recessive inheritance

UUID: 29f62558-f8d5-4060-8180-f46d31f8443b

Approved on: 2026-08-18

Published on: 2026-08-19

HGVS expressions

NM_000419.5:c.2315C>G

NC_000017.11:g.44376341G>C

CM000679.2:g.44376341G>C

NC_000017.10:g.42453709G>C

CM000679.1:g.42453709G>C

NC_000017.9:g.39809235G>C

NG_008331.1:g.18165C>G

ENST00000262407.6:c.2315C>G

ENST00000648408.1:c.1746C>G

ENST00000262407.5:c.2315C>G

ENST00000592462.5:n.1110C>G

NM_000419.3:c.2315C>G

NM_000419.4:c.2315C>G

Uncertain Significance

PP4_Moderate

BS1 BP4 PP3 PM2 PM3

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_000419.5(ITGA2B):c.2315C>G (p.Pro772Arg) missense variant has been reported in at least one patient (Patient 7 in PMID:19172520/GT database record 164) who displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). Additionally, αIIbβ3 surface expression was reduced to <10%, as measured by flow cytometry. 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: PP4_Moderate (VCEP specifications version 2.1).

PP4_Moderate

At least one patient (Patient 7 in PMID:19172520/GT database record 164) with this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). Additionally, αIIbβ3 surface expression was reduced to <10%, as measured by flow cytometry. However, ITGA2B and ITGB3 were not sequenced across all exons and intron/exon boundaries.

BS1

The highest population minor allele frequency in gnomAD v4.1 is 0.0002416 (22/91078 alleles) in the South Asian population. This intermediate allele frequency is lower than the ClinGen PD VCEP threshold (>0.00158) for BS1 but higher than the threshold (<0.0001) for PM2_Supporting.

BP4

The computational predictor REVEL gives a score of 0.321, which is above the ClinGen PD VCEP threshold of <0.25.

PP3

The computational predictor REVEL gives a score of 0.321, which is below the ClinGen PD VCEP PP3 threshold of >0.7 and does not predict a damaging effect on ITGA2B function. And the computational splicing predictor SpliceAI indicated that the variant has no predicted impact on splicing.

PM2

PM3

The authors report the variant c.2315C>G in patient 7 (PMID: 19172520), the GT database (record 164) confirms it is homozygous. Allele frequency is too high (>PM2) to consider here. 0pt

Curation History

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