ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.1389C>T (p.Tyr463=)

gnomAD frequency: 0.00001  dbSNP: rs148618973
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen RCV001122503 SCV004037408 likely benign Glanzmann thrombasthenia 2023-08-15 reviewed by expert panel curation The NM_000419.5(ITGA2B):c.1389C>T (p.Tyr463=) synonymous variant was observed by Illumina as part of a predisposition screen in an ostensibly healthy population. After a comprehensive literature search, the synonymous variant has not identified with any individuals with Glanzmann Thrombasthenia. The highest population minor allele frequency in gnomAD v2.1.1 is 0.0001230 (2/16254 alleles) in the African/African American population but the gnomAD v3.2.1 African/African American population has an additional 28728 alleles (non-overlapping with v2.1.1) with no occurrences of this variant. Overall, there is a frequency of 2/44,982 = 0.000044 which is lower than the ClinGen PD VCEP threshold <0.0001 for PM2_Supporting. In silico predictor SpliceAI revealed that the intronic mutation is not expected to impact splicing and a PhyloP score of 0.46 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: PM2_supporting, BP4 and BP7 (PD VCEP specifications version 2.1).
Illumina Laboratory Services, Illumina RCV001122503 SCV001281222 uncertain significance 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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