Submissions for variant NM_000212.3(ITGB3):c.325del (p.Val109fs)

dbSNP: rs1567764064

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV000761244	SCV005061682	likely pathogenic	Glanzmann thrombasthenia	2024-05-02	reviewed by expert panel	curation	The frameshift variant NM_000212.3(ITGB3):c.325del (p.Val109SerfsTer?) is predicted to cause a premature stop codon in biologically-relevant-exon 4/15 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established mechanism (PVS1). The variant is absent from gnomADv4.0.0 (PM2_supporting). The variant has been found in at least one individual with GT, ClinVar entry (SCV000891200.1) by the Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota. The patient is compound heterozygous with variant of uncertain significance NM_000212.3(ITGB3):c.778-2A>G, phasing not confirmed. The patient had bleeding since childhood, abnormal aggregation, and flow cytometry low levels of GPIIb/IIIa. Patient information is consistent with GT but insufficient for PP4. In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1 and PM2_supporting (VCEP specifications version 2.1.0).
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota	RCV000761244	SCV000891200	likely pathogenic	Glanzmann thrombasthenia	2017-12-21	criteria provided, single submitter	clinical testing