Submissions for variant NM_000212.3(ITGB3):c.72C>T (p.Gly24=)

gnomAD frequency: 0.00052  dbSNP: rs768269394

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV001123374	SCV003934986	likely benign	Glanzmann thrombasthenia	2023-06-01	reviewed by expert panel	curation	After a comprehensive literature search of the synonymous variant NM_000212.3(ITGB3):c.72C>T (p.Gly24=), no individuals with Glanzmann thrombasthenia were reported with the variant and has only been observed in a ostensibly healthy population. The variant has a minor allele frequency of 0.00110 (18/16424 alleles) in the South Asian population in gnomAD, which does not meet our threshold criteria for PM2_supporting or BS1. In silico predictor SpliceAI revealed that the synonymous mutation is not expected to impact splicing and a PhyloP score of -0.28 shows that the nucleotide position is not highly conserved (BP4, BP7). In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BP4, BP7 (PD VCEP specifications version 2.1).
Illumina Laboratory Services, Illumina	RCV001123374	SCV001282209	benign	Glanzmann thrombasthenia	2018-01-13	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	RCV002556664	SCV003245143	likely benign	not provided	2025-01-06	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV002556664	SCV004140772	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	ITGB3: BP4, BP7