Submissions for variant NM_000419.5(ITGA2B):c.439C>G (p.Leu147Val)

gnomAD frequency: 0.00936  dbSNP: rs76066357

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV000860829	SCV003915982	benign	Glanzmann thrombasthenia	2023-02-02	reviewed by expert panel	curation	The NM_000419.5:c.439C>G variant in ITGA2B is a missense variant predicted to cause substitution of Leucine by Valine at amino acid 147 (p.Leu147Val). The highest population minor allele frequency in gnomAD v2.1.1 is 0.01420 (1822/128308 alleles) in the European (non-Finnish) population, which is higher than the ClinGen PD VCEP threshold (>0.0024) for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.053, which is below the ClinGen PD VCEP threshold of <0.25 and predicts no damaging effect on ITGA2B function (BP4). This variant is also classified as Benign/Likely benign in ClinVar and was observed as part of a predisposition screen in an ostensibly healthy population by Illumina. In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1 and BP4 (VCEP specifications version 2).
PreventionGenetics, part of Exact Sciences	RCV000244527	SCV000304088	benign	not specified		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000860829	SCV001000993	benign	Glanzmann thrombasthenia	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000860829	SCV001285427	likely benign	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Genetic Services Laboratory, University of Chicago	RCV000244527	SCV002072069	benign	not specified	2020-06-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV002274952	SCV002563417	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	ITGA2B: BP4, BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV002274952	SCV005212882	likely benign	not provided		criteria provided, single submitter	not provided