Submissions for variant NM_000419.5(ITGA2B):c.574+5G>A

dbSNP: rs1598383011

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV000851829	SCV005061702	uncertain significance	Glanzmann thrombasthenia	2024-06-06	reviewed by expert panel	curation	The c.574+5G>A variant in ITGA2B is an intronic variant in intron 4. This variant has been detected in the homozygous form in at least 1 proband in the ThromboGenetics cohort (TGP0375, PMID:31064749) Total points: 0.5 (PM3_Supporting). TGP0375 was not reported with supporting phenotypic information and did not meet criteria for PP4 (PMID:31064749).This variant is absent from gnomAD v4.1.0 (PM2_Supporting). The computational splicing predictor SpliceAI gives a score of 0.8 for donor loss, predicting that the variant disrupts the donor splice site of intron 4 (PP3). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_Supporting, PP3, PM3_supporting. (VCEP specifications version 2; date of approval 06/06/2024)
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000851829	SCV000899813	likely pathogenic	Glanzmann thrombasthenia	2019-02-01	criteria provided, single submitter	research