Submissions for variant NM_000419.5(ITGA2B):c.2188-7C>G

gnomAD frequency: 0.38774  dbSNP: rs850730

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV000340302	SCV004037412	benign	Glanzmann thrombasthenia	2023-09-07	reviewed by expert panel	curation	After a comprehensive literature search of the intronic variant NM_000419.5(ITGA2B):c.2188-7C>G, no individuals with Glanzmann Thrombasthenia were reported with the variant. The variant has a high minor allele frequency of 0.4311 (6420/14892 alleles) in the East Asian population, which is higher than the ClinGen PD VCEP threshold (>0.0024), and therefore meets benign criterion (BA1). In silico predictor spliceAI revealed that the intronic mutation is not expected to impact splicing and a PhyloP score of 0.287 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 and BP7 (PD VCEP specifications version 2.1).
PreventionGenetics, part of Exact Sciences	RCV000241554	SCV000304085	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000340302	SCV000403365	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	RCV000340302	SCV001717672	benign	Glanzmann thrombasthenia	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001539295	SCV001757049	benign	not provided	2018-11-12	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001730609	SCV001980745	benign	Glanzmann thrombasthenia 1	2021-08-19	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001539295	SCV005253395	benign	not provided		criteria provided, single submitter	not provided