Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV001123376 | SCV001809890 | benign | Glanzmann thrombasthenia | 2023-12-19 | reviewed by expert panel | curation | The NM_000212.3(ITGB3):c.197T>G (p.Leu66Arg) missense variant was observed by Illumina as part of a predisposition screen in an ostensibly healthy population and has been reported in the literature in a blood donor cohort (PMID: 32110192) but has not been reported in a GT patient. There is not consensus among computational evidence as to whether there is an effect on the gene or gene product. The variant occurs at a frequency in gnomAD v4.0.0 of 0.002756 (3252/1180038 alleles) in the European (non-Finnish) population, which is higher than the ClinGen PD VCEP BA1 threshold (>0.0024), and therefore meets this criterion (BA1). In summary this variant meets criteria for classification as Benign for Glanzmann thrombasthenia. GT-specific criteria applied: BA1. |
| Invitae | RCV000860861 | SCV001001030 | likely benign | not provided | 2024-01-31 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001123376 | SCV001282211 | 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689904 | SCV005185571 | benign | not specified | 2024-05-30 | criteria provided, single submitter | clinical testing | Variant summary: ITGB3 c.197T>G (p.Leu66Arg) results in a non-conservative amino acid change located in the PSI domain (IPR016201) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0018 in 282772 control chromosomes, predominantly at a frequency of 0.0037 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in ITGB3 causing Glanzmann Thrombasthenia 2 phenotype. To our knowledge, no occurrence of c.197T>G in individuals affected with Glanzmann Thrombasthenia 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 695335). Based on the evidence outlined above, the variant was classified as benign. |
| Birmingham Platelet Group; University of Birmingham | RCV001270572 | SCV001450871 | uncertain significance | Abnormal bleeding; Thrombocytopenia | 2020-05-01 | no assertion criteria provided | research |