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]

Link to SEPIO compliant JSON-LD document

CA8602528

Gene: ITGA2B

Condition: Glanzmann's thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 61cd22cd-dfd2-4583-86bb-088a1cea234f

HGVS expressions

NM_000419.5:c.2929C>T

NM_000419.3:c.2929C>T

NM_000419.4:c.2929C>T

ENST00000262407.5:c.2929C>T

ENST00000587295.5:n.253+1160C>T

ENST00000588098.1:n.23C>T

ENST00000592462.5:n.2440C>T

NC_000017.11:g.44374673G>A

CM000679.2:g.44374673G>A

NC_000017.10:g.42452041G>A

CM000679.1:g.42452041G>A

NC_000017.9:g.39807567G>A

NG_008331.1:g.19833C>T

Pathogenic

PVS1 PP4_Moderate PM2_Supporting PM3_Supporting

Evidence Links 1

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

The NM_000419.5:c.2929C>T (p.Arg977Ter) nonsense variant occurs in exon 28 of 30 and is predicted to result in NMD. The variant is at an extremely low frequency of 0.00003266 in the South Asian population. The variant is reported in one compound heterozygous with pathogenic variant Pro176Ala individual who meets criteria for PP4 (PMID: 10607701). In summary, based on the evidence available at this time, the variant is classified as pathogenic. GT-specific criteria applied: PVS1, PM2_Supporting, PM3_Supporting, and PP4_Moderate.

PVS1

The Arg977Ter nonsense variant occurs in exon 28 or 30 and is predicted to result in NMD.

PP4_Moderate

At least one proband from PMID: 10607701 meets the criteria for PP4; including mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin.

PM2_Supporting

This variant is at an extremely low frequency (below the <1/10,000 threshold) with an overall allele frequency from gnomAD of 0.000007973 and MAF of 0.00003266 (1/30,616 alleles) in the South Asian population.

PM3_Supporting

This variant has been reported once in a compound heterozygote (PMID: 10607701) with pathogenic variant Pro176Ala. Two additional patients have been reported in (PMIDs: 12083483 and 20020534) but second variants were not identified.

PubMed:10607701

Approved on: 2020-09-06

Published on: 2021-01-28

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