Submissions for variant NM_000419.5(ITGA2B):c.2992del (p.Trp998fs)

dbSNP: rs1598375578

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV000852099	SCV001809906	uncertain significance	Glanzmann thrombasthenia	2024-06-06	reviewed by expert panel	curation	The NM_000419.5(ITGA2B):c.2992del (p.Trp998GlyfsTer?) variant causes a frameshift and subsequent stop loss, resulting in alteration of the remaining 42 amino acids followed by the addition of 90 amino acids to the ITGA2B protein. This alters the transmembrane domain of the protein which is considered a critical region for protein function by the Platelet Disorders VCEP (PVS1_strong). This variant is absent from gnomAD v4.0 (PM2_Supporting). Patient TGP0655, of PMID: 31064749, is compound heterozygous for c.409-1G>A (classified Likely Pathogenic by the PD VCEP) and c.2992del, however confirmation of trans phase and sufficient phenotypic information were not available for this patient to meet any criteria. In summary, this variant is classified as uncertain significance for autosomal recessive Glanzmann thrombasthenia. GT-specific criteria applied: PVS1_Strong, PM2_Supporting.
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000852099	SCV000899656	pathogenic	Glanzmann thrombasthenia	2019-02-01	criteria provided, single submitter	research