ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.224del (p.Gly75fs)

dbSNP: rs1567906131
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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 RCV002254826 SCV002525922 likely pathogenic Glanzmann thrombasthenia 2022-06-13 reviewed by expert panel curation The c.224del (p.Gly75AlafsTer36) variant in exon 2 is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 3/30 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00002970 (1/33668 alleles) in the Latino/Admixed American population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). This variant has not been reported in patients with GT in the literature, to the best of our knowledge. In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1, PM2_Supporting. (VCEP specifications version 2; date of approval: April 7, 2022)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003230741 SCV003928974 likely pathogenic ITGA2B-related disorder 2023-04-12 criteria provided, single submitter clinical testing Variant summary: ITGA2B c.224delG (p.Gly75AlafsX36) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic in ClinVar. The variant allele was found at a frequency of 4.3e-06 in 233746 control chromosomes (gnomAD). To our knowledge, no occurrence of c.224delG in individuals affected with ITGA2B-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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