Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV001225264 | SCV001397528 | uncertain significance | Glanzmann thrombasthenia | 2023-06-01 | reviewed by expert panel | curation | The ITGA2B c.188+8del variant has been reported in at least one GT proband (PMID: 19691478). GT14 meets the criteria for PP4_moderate, including mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin. An intermediate allele frequency is reported by gnomAD, for the South Asian subpopulation the MAF is 0.0002613 (8/30616). In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PP4_moderate (VCEP specifications version 2). |
| Labcorp Genetics |
RCV001225264 | SCV003512592 | likely benign | Glanzmann thrombasthenia | 2022-08-29 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317459 | SCV004020608 | uncertain significance | not specified | 2023-06-23 | criteria provided, single submitter | clinical testing | Variant summary: ITGA2B c.188+8delG alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-05 in 251098 control chromosomes. c.188+8delG has been reported in the literature in at least 1 heterozygous individual affected with Glanzmann thrombasthenia 1 (example: Kannan_2009). These report(s) do not provide unequivocal conclusions about association of the variant with Glanzmann thrombasthenia 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 19691478). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely benign, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |