Submissions for variant NM_000212.3(ITGB3):c.1545G>A (p.Arg515=)

gnomAD frequency: 0.28592  dbSNP: rs4634

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV000394843	SCV003916009	benign	Glanzmann thrombasthenia	2023-01-17	reviewed by expert panel	curation	After a comprehensive literature search of the synonymous variant NM_000212.3(ITGB3):c.1545G>A (p.Arg515=), no individuals with Glanzmann thrombasthenia were reported with the variant. Moreover, the variant has a minor allele frequency of 0.3455 (6891/19946 alleles) in gnomAD, found in the East Asian population, which is considerably higher than the expected frequency of the disease(BA1). In silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing and a PhyloP score of 0.285 shows that the nucleotide position is not highly conserved (BP4, BP7). 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, BP4, BP7 (PD VCEP specifications version 2.1).
PreventionGenetics, part of Exact Sciences	RCV000241947	SCV000302997	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000394843	SCV000403741	benign	Glanzmann thrombasthenia	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001517498	SCV001726009	benign	not provided	2025-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001517498	SCV001942580	benign	not provided	2021-06-09	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001517498	SCV005249349	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000241947	SCV001743527	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000241947	SCV001955779	benign	not specified		no assertion criteria provided	clinical testing