Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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  • See Evidence submitted by expert panel for details.

CA8602943

Gene: ITGA2B
Condition: Glanzmann thrombasthenia
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: d1bfa84e-8830-48b7-87d3-8c4f3d32ce7e

HGVS expressions

NM_000419.5:c.1769G>A
NC_000017.11:g.44379798C>T
CM000679.2:g.44379798C>T
NC_000017.10:g.42457166C>T
CM000679.1:g.42457166C>T
NC_000017.9:g.39812692C>T
NG_008331.1:g.14708G>A
ENST00000262407.6:c.1769G>A
ENST00000648408.1:n.1200G>A
ENST00000262407.5:c.1769G>A
ENST00000592462.5:n.564G>A
NM_000419.3:c.1769G>A
NM_000419.4:c.1769G>A

Uncertain Significance

Met criteria codes 1
PP4_Moderate
Not Met criteria codes 4
BS1 PP3 PM3 PM2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Platelet Disorders VCEP
The NM_000419.5(ITGA2B):c.1769G>A (p.Arg590Gln) has been reported in one patient with suspected type 3 GT (PMID: 29675921). Based on the evidence available at this time, the variant is classified as uncertain significance. No GT-specific criteria applied: PP4_moderate.
Met criteria codes
PP4_Moderate
GT39 of PMID: 29675921 meets the criteria for PP4_moderate; including mucocutaneous bleeding, and impaired aggregation with all agonists except ristocetin. There was reduced function of αIIbβ3 measured by flow cytometry, however 43% PAC-1 binding was not considered sufficient to meet PP4_strong. ITGA2B and ITGB3 were sequenced across all exons and intron/exon boundaries.
Not Met criteria codes
BS1
This variant occurs at an intermediate allele frequency, with an overall allele frequency in gnomAD of 0.00005189 and a MAF of 0.0002314 (8/34,568 alleles) in the Latino population. This is below the BS1 threshold of >0.00158 but above the PM2 threshold of <0.0001.
PP3
SIFT, PolyPhen2, and MutationTaster agree that there is a deleterious effect. However, the REVEL score for this variant is 0.361, which does not meet the VCEP-established threshold of >0.7 to support a deleterious effect. Additionally, no impact on splicing is predicted.
PM3
GT39 is compound heterozygous for Cys857Phe (VUS) and Arg590Gln, confirmation of trans phase was not reported. 0pt
PM2
This variant occurs at an intermediate allele frequency, with an overall allele frequency in gnomAD of 0.00005189 and a MAF of 0.0002314 (8/34,568 alleles) in the Latino population. This is below the BS1 threshold of >0.00158 but above the PM2 threshold of <0.0001.
Approved on: 2021-07-08
Published on: 2021-08-19
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