Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000778835 | SCV000915228 | uncertain significance | Platelet-type bleeding disorder 10 | 2018-11-21 | criteria provided, single submitter | clinical testing | The CD36 c.380C>G (p.Ser127Ter) variant is a stop-gained variant predicted to result in premature termination of the protein, which was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for this disease. |
| Laboratory for Molecular Medicine, |
RCV004017735 | SCV004847280 | likely pathogenic | Inherited bleeding disorder, platelet-type | 2023-03-24 | criteria provided, single submitter | clinical testing | The p.Ser127X variant in CD36 has not been reported in individuals with CD36-related disorder but it has been reported in ClinVar (Variation ID 632008). It has also been identified in 4/68038 European chromosomes by gnomAD v3.1.2 (http://gnomad.broadinstitute.org). This nonsense variant leads to a premature termination codon at position 127, which is predicted to lead to a truncated or absent protein. Loss of function of the CD36 gene is an established disease mechanism in autosomal recessive Platelet glycoprotein IV deficiency. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive platelet glycoprotein IV deficiency. ACMG/AMP Criteria applied: ACMG: PVS1, PM2_Supporting |