Submissions for variant NM_001001548.3(CD36):c.332_333del (p.Thr111fs)

dbSNP: rs572295823

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	RCV000490431	SCV000267242	pathogenic	Platelet-type bleeding disorder 10	2016-03-18	criteria provided, single submitter	reference population
Illumina Laboratory Services, Illumina	RCV000490431	SCV000915227	pathogenic	Platelet-type bleeding disorder 10	2018-10-05	criteria provided, single submitter	clinical testing	The CD36 c.332_333delCA (p.Thr111SerfsTer22) variant results in a frameshift and is predicted to result in premature termination of the protein. The p.Thr111SerfsTer22 variant has been reported in at least five studies in which it is found in at least twelve individuals with platelet glycoprotein IV deficiency, including in one in a homozygous state, in five in a compound heterozygous state, and in at least five in a heterozygous state, and in one additional individual with unknown zygosity (Kashiwagi et al. 1994; Yanai et al. 2000; Xu et al. 2013; Li et al. 2015; Masuda et al. 2015). In these studies, all the individuals are reported as generally healthy but failing to express CD36 on their platelets. The p.Thr111SerfsTer22 variant has been described as one of the most common variants associated with platelet glycoprotein IV deficiency in the Southern Chinese population (Xu et al. 2013). The variant was also found in a heterozygous state in three individuals with cerebral malaria (Omi et al. 2002). Control data are unavailable for this variant, which is reported at a frequency of 0.018849 in the East Asian population of the 1000 Genomes Project. Flow cytometry found four of the heterozygous patients were negative for CD36 expression and one heterozygote had a normal phenotype but had significantly reduced CD36 expression (Li et al. 2015; Masuda et al. 2015). Based on the collective evidence, the p.Thr111SerfsTer22 variant is classified as pathogenic for platelet glycoprotein IV deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Genetics and Molecular Pathology, SA Pathology	RCV000490431	SCV002556855	pathogenic	Platelet-type bleeding disorder 10	2021-04-22	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002503831	SCV002804913	pathogenic	Platelet-type bleeding disorder 10; Coronary heart disease, susceptibility to, 7; Malaria, susceptibility to	2021-10-26	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV002503831	SCV005415792	pathogenic	Platelet-type bleeding disorder 10; Coronary heart disease, susceptibility to, 7; Malaria, susceptibility to		criteria provided, single submitter	clinical testing	BS1+PVS1+PM3_VeryStrong+PP4
Reproductive Health Research and Development, BGI Genomics	RCV000490431	SCV001142371	pathogenic	Platelet-type bleeding disorder 10	2020-01-06	no assertion criteria provided	curation	NM_001001547.2:c.332_333delCA in the CD36 gene has an allele frequency of 0.016 in East Asian subpopulation in the gnomAD database. The CD36 c.332_333delCA (p.Thr111SerfsTer22) variant results in a frameshift and is predicted to result in premature termination of the protein. The p.Thr111SerfsTer22 variant has been reported in individuals with platelet glycoprotein IV deficiency, including in one in a homozygous state, in five in a compound heterozygous state with 1228_1239del, Arg386Trp, Gln74Term (PMID: 23966019; 25330908; 25798958). Taken together, we interprete this variant as Pathogenic/Likely pathogenic variant. ACMG/AMP Criteria applied: PVS1; PP4; PM3_Strong.