Submissions for variant NM_000212.3(ITGB3):c.444C>G (p.Tyr148Ter)

dbSNP: rs887221055

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV004577562	SCV005061673	pathogenic	Glanzmann thrombasthenia	2024-04-16	reviewed by expert panel	curation	The c.444C>G (p.Tyr148Ter) variant in exon 4 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 4 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). The highest population minor allele frequency in gnomAD v4.0.0 is 0.000001799] (2/1112006 alleles) in the European (non-Finnish) population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). This variant is reported in ClinVar (SCV002515562.1) in a homozygous Glanzmann thrombasthenia patient (PM3_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1, PM3_Supporting and PM2_Supporting (VCEP specifications version 2; date of approval 04/16/2024.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002245360	SCV002515562	pathogenic	Glanzmann thrombasthenia 1		no assertion criteria provided	clinical testing