Submissions for variant NM_000419.5(ITGA2B):c.2929C>T (p.Arg977Ter)

gnomAD frequency: 0.00001  dbSNP: rs79657230

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV001225251	SCV001397503	pathogenic	Glanzmann thrombasthenia	2020-09-06	reviewed by expert panel	curation	The NM_000419.5:c.2929C>T (p.Arg977Ter) nonsense variant occurs in exon 28 of 30 and is predicted to result in NMD. The variant is at an extremely low frequency of 0.00003266 in the South Asian population. The variant is reported in one compound heterozygous with pathogenic variant Pro176Ala individual who meets criteria for PP4 (PMID: 10607701). In summary, based on the evidence available at this time, the variant is classified as pathogenic. GT-specific criteria applied: PVS1, PM2_Supporting, PM3_Supporting, and PP4_Moderate.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001225251	SCV003441985	pathogenic	Glanzmann thrombasthenia	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg977*) in the ITGA2B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ITGA2B are known to be pathogenic (PMID: 21917754). This variant is present in population databases (rs79657230, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Glanzmann thrombasthenia (PMID: 14687991, 32237906). This variant is also known as R946X. ClinVar contains an entry for this variant (Variation ID: 953019). For these reasons, this variant has been classified as Pathogenic.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002245883	SCV002515509	pathogenic	Platelet-type bleeding disorder 16		no assertion criteria provided	research