ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.1958C>T (p.Pro653Leu)

gnomAD frequency: 0.00004  dbSNP: rs375936260
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen RCV000341629 SCV004037422 uncertain significance Glanzmann thrombasthenia 2023-08-15 reviewed by expert panel curation After a comprehensive literature search, the NM_000419.5(ITGA2B):c.1958C>T (p.Pro653Leu) variant has not been identified in any individuals with Glanzmann thrombasthenia. The variant is has a low minor allele frequency, the highest being 0.000008914 (1/112184 alleles) in the European (Non-Finnish) population (<1/10,000; PM2_supporting). The computational predictor REVEL gives a score of 0.217, predicting no deleterious effect on gene function (BP4). In summary, this variant meets the criteria to be classified as variant of uncertain significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_supporting and BP4 (PD VCEP specifications version 2.1).
Illumina Laboratory Services, Illumina RCV000341629 SCV000403368 uncertain significance 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, 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.
Ambry Genetics RCV004021705 SCV004889454 uncertain significance Inborn genetic diseases 2023-12-28 criteria provided, single submitter clinical testing The c.1958C>T (p.P653L) alteration is located in exon 20 (coding exon 20) of the ITGA2B gene. This alteration results from a C to T substitution at nucleotide position 1958, causing the proline (P) at amino acid position 653 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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