ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.2471C>G (p.Thr824Ser)

gnomAD frequency: 0.00003  dbSNP: rs780567683
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen RCV001122399 SCV004190249 uncertain significance Glanzmann thrombasthenia 2023-10-17 reviewed by expert panel curation The c.2471C>G variant in ITGA2B is a missense variant predicted to cause substitution of Threonine by Serine at amino acid 824 (p.Thr824Ser). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00001552 (2/128896 alleles) in the European (non-Finnish) population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). The computational predictor REVEL gives a score of 0.127, which is below the ClinGen PD VCEP threshold of <0.25 and predicts no damaging effect on ITGA2B function (BP4). Due to conflicting evidence, this variant is classified as a variant of unknown significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD-VCEP: PM2_Supporting and BP4 (VCEP specifications version 2).
Illumina Laboratory Services, Illumina RCV001122399 SCV001281113 uncertain significance Glanzmann thrombasthenia 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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