Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV003605766 | SCV005439092 | uncertain significance | Glanzmann thrombasthenia | 2024-10-15 | reviewed by expert panel | curation | The c.118A>G (p.Thr40Ala variant in ITGA2B is a missense variant predicted to cause substitution of threonine by alanine at amino acid 40 .It has been reported in ClinVar in association with possible Glanzmann Thrombastheina (affected status: unknown). After a thorough literature search, this variant was not found to be published in any patients with Glanzmann Thrombasthenia. The highest population minor allele frequency in gnomAD v4.1.0 is 0.0002830 (334/1180028 alleles) in the European (non-Finnish) population. This intermediate allele frequency is lower than the ClinGen PD VCEP threshold (>0.00158) for BS1 but higher than the threshold (<0.0001) for PM2_Supporting. The computational predictor REVEL gives a score of 0.232, which is below the ClinGen PD VCEP threshold of <0.25 and predicts no damaging effect on ITGA2B function (BP4). In summary, this variant meets the criteria to be classified as a variant of unknown significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BP4. |
| Gene |
RCV001752051 | SCV001986774 | uncertain significance | not provided | 2024-03-21 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002539921 | SCV003645889 | uncertain significance | Inborn genetic diseases | 2021-08-17 | criteria provided, single submitter | clinical testing | The c.118A>G (p.T40A) alteration is located in exon 1 (coding exon 1) of the ITGA2B gene. This alteration results from a A to G substitution at nucleotide position 118, causing the threonine (T) at amino acid position 40 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003605766 | SCV004463523 | uncertain significance | Glanzmann thrombasthenia | 2024-03-07 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 40 of the ITGA2B protein (p.Thr40Ala). This variant is present in population databases (rs77120952, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ITGA2B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1304284). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ITGA2B protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |