Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV001290471 | SCV001478508 | uncertain significance | Glanzmann thrombasthenia | 2024-01-04 | reviewed by expert panel | curation | NM_000212.3(ITGB3):c.1732G>A (p.Asp578Asn) is a missense variant which has been reported in at least one proband (GT3) by PMID:25728920. This variant has been reported to occur in cis with a platelet disorder VCEP classified Pathogenic variant (p.Ser237CysfsTer13; BP2). The highest population minor allele frequency in gnomAD v4.0.0 is 0.002137 (13/6084 alleles) in the Middle Eastern population, which is higher than the ClinGen PD VCEP threshold (>0.00158), and therefore meets this criterion (BS1). In silico tools (REVEL score =0.81) predict a deleterious effect on the gene product (PP3). GT specific criteria applied are BS1, BP2 and PP3 and this variant is classified as a variant of uncertain significance for autosomal recessive Glanzmann thrombasthenia. |
| Breakthrough Genomics, |
RCV004692407 | SCV005192939 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004770008 | SCV005381518 | uncertain significance | not specified | 2024-08-12 | criteria provided, single submitter | clinical testing | Variant summary: ITGB3 c.1732G>A (p.Asp578Asn) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 251382 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1732G>A has been reported in the literature in at least an individual affected with Glanzmann Thrombasthenia 2 where it was seen in cis with another pathogenic variant (example: Nurden_2014) These report(s) do not provide unequivocal conclusions about association of the variant with Glanzmann Thrombasthenia 2. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 25728920, 27469266, 37647632). ClinVar contains an entry for this variant (Variation ID: 996177). Based on the evidence outlined above, the variant was classified as uncertain significance. |