ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.3076C>T (p.Arg1026Trp) (rs766503255)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Platelet Disorders Variant Curation Expert Panel,ClinGen RCV001003530 SCV001397532 uncertain significance Glanzmann thrombasthenia 2020-06-16 reviewed by expert panel curation The NM_000419.5:c.3076C>T variant results in the Arg1026Trp missense change. It is absent in population databases and is predicted damaging by in silico tools (REVEL score of 0.897). All the individuals with this variant, reported in the literature, are heterozygous and have macrothrombocytopenia with or without a mild bleeding tendency (PMID: 31119735, 21454453, 31064749). In summary, there is insufficient evidence at this time to classify the Arg1026Trp variant. GT-specific criteria applied: PM2_Supporting, PP3.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000851592 SCV000899328 pathogenic Thrombocytopenia 2019-02-01 criteria provided, single submitter research
Invitae RCV001003530 SCV001230135 pathogenic Glanzmann thrombasthenia 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1026 of the ITGA2B protein (p.Arg1026Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with autosomal dominant thrombocytopenia (PMID: 21454453, 29090484, 31119735). It has also been observed to segregate with disease in related individuals. This variant is also known as p.R995W in the literature. ClinVar contains an entry for this variant (Variation ID: 50233). This variant has been reported to affect ITGA2B protein function (PMID: 21454453). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV001003530 SCV001530357 pathogenic Glanzmann thrombasthenia 2018-11-23 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing in multiple individuals [PMID 21454453, 29090484]
OMIM RCV000043486 SCV000067298 pathogenic Platelet-type bleeding disorder 16 2011-05-19 no assertion criteria provided literature only
NIHR Bioresource Rare Diseases, University of Cambridge RCV000851592 SCV001161856 pathogenic Thrombocytopenia 2019-09-01 no assertion criteria provided research The clinical significance is unchnaged from the previous submission.
Biochemical Molecular Genetic Laboratory,King Abdulaziz Medical City RCV000043486 SCV001190807 pathogenic Platelet-type bleeding disorder 16 2020-02-05 no assertion criteria provided clinical testing

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