ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.889G>C (p.Ala297Pro)

dbSNP: rs531610168
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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 RCV001225237 SCV001397487 likely pathogenic Glanzmann thrombasthenia 2024-09-05 reviewed by expert panel curation The NM_000419.4:c.889G>C variant that results in the Ala297Pro amino acid change is seen in one unpublished homozygous GT individual with mild mucocutaneous bleeding symptoms and lack of platelet aggregation in response to ADP, collagen, U46619, AA and TRAP, but normal response to ristocetin (PP4_moderate). As well as their affected homozygous sibling (PP1). A second homozygous individual has also been reported (PM3; PMID: 32089034). The variant is reported in gnomADv4.1 at a frequency of 0.00004392 (4/91080 alleles) in the South Asian population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). In summary, based on the available evidence at this time, the variant is classified as likely pathogenic for GT. GT-specific criteria applied: PM2_Supporting, PM3, PP1, and PP4_Moderate.
Labcorp Genetics (formerly Invitae), Labcorp RCV001225237 SCV004632643 uncertain significance Glanzmann thrombasthenia 2023-09-27 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 953005). This missense change has been observed in individuals with Glanzmann thrombasthenia (PMID: 32089034; Invitae). This variant is present in population databases (rs531610168, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 297 of the ITGA2B protein (p.Ala297Pro).

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