Submissions for variant NM_000419.5(ITGA2B):c.2556G>C (p.Gln852His)

dbSNP: rs2048538187

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV001122397	SCV004190235	uncertain significance	Glanzmann thrombasthenia	2023-10-17	reviewed by expert panel	curation	The c.2556G>C variant in ITGA2B is a missense variant predicted to cause substitution of Glutamine by Histidine at amino acid (p.Gln852His). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.051, which is below the ClinGen PD VCEP threshold of <0.25 and predicts no damaging effect on ITGA2B function (BP4). This variant was observed by Illumina as part of a predisposition screen in an ostensibly healthy population, however, no cases of the variant segregating with Glanzmann thrombasthenia were found in the literature. Due to conflicting evidence, this variant is classified as a variant of unknown significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD-VCEP: PM2_Supporting and BP4 (VCEP specifications version 2).
Illumina Laboratory Services, Illumina	RCV001122397	SCV001281111	uncertain significance	Glanzmann thrombasthenia	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.