Submissions for variant NM_000419.5(ITGA2B):c.409-3C>G

dbSNP: rs2143489585

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV003464413	SCV004190247	uncertain significance	Glanzmann thrombasthenia	2023-10-17	reviewed by expert panel	curation	The NM_000419.5(ITGA2B):c.409-3C>G intronic variant was identified in a patient with a clinical diagnosis of GT, but insufficient information to be highly specific, and is predicted to impact splicing through loss of an acceptor site. Splicing was predicted to be impacted with the loss of an acceptor site by Splice AI (0.72) and varSEAK (PP3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was homozygous in the reported individual (Patient 8, PMID: 31029159) with a clinical diagnosis of GT. Since this was a homozygous occurrence and this variant was not seen in the literature elsewhere; per SVI recommendations this receives 0.5pt since this variant has a MAF of <0.0001 (PM3_Supporting). This variant was identified as heterozygous in parents and not homozygous in healthy individuals in the family. In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_supporting, PM3_Supporting, PP3 (VCEP specifications version 2.1).
3billion	RCV002250914	SCV002521119	uncertain significance	Glanzmann thrombasthenia 1	2022-05-22	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. In silico tools predict the variant to alter splicing and produce an abnormal transcript (SpliceAI: 0.72). Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline.