Submissions for variant NM_000212.3(ITGB3):c.285C>T (p.Leu95=)

gnomAD frequency: 0.00030  dbSNP: rs151121691

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV001123379	SCV001809912	likely benign	Glanzmann thrombasthenia	2021-05-07	reviewed by expert panel	curation	The NM_000212.3(ITGB3):c.285C>T (p.Leu95=) synonymous variant was observed by Illumina as part of a predisposition screen in an ostensibly healthy population and has been reported in the literature in a blood donor cohort (PMID: 32110192) but has not been reported in a GT patient. It is not predicted to have an impact on splicing and occurs at an intermediate allele frequency of 0.0004338 (56/129078 alleles) in the gnomAD non-Finnish European population. In summary, this variant meets criteria to be classified as Likely Benign for GT. GT-specific criteria applied: BS1, BP4, and BP7.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000862487	SCV001002998	likely benign	not provided	2025-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001123379	SCV001282214	uncertain significance	Glanzmann thrombasthenia	2018-02-09	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genetic Services Laboratory, University of Chicago	RCV001816947	SCV002067073	likely benign	not specified	2019-01-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003948071	SCV004758675	likely benign	ITGB3-related disorder	2019-12-30	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).