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.
ClinVar Genomic variation as it relates to human health
NM_001001548.3(CD36):c.332_333del (p.Thr111fs)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(5)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic
5
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001001548.3(CD36):c.332_333del (p.Thr111fs)
Variation ID: 225309 Accession: VCV000225309.9
- Type and length
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Microsatellite, 2 bp
- Location
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Cytogenetic: 7q21.11 7: 80661110-80661111 (GRCh38) [ NCBI UCSC ] 7: 80290426-80290427 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline May 25, 2017 Dec 31, 2022 Oct 26, 2021 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001001548.3:c.332_333del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001001548.1:p.Thr111fs frameshift NM_000072.3:c.332_333del NP_000063.2:p.Thr111fs frameshift NM_000072.3:c.332_333delCA NM_001001547.3:c.332_333del NP_001001547.1:p.Thr111fs frameshift NM_001127443.2:c.332_333del NP_001120915.1:p.Thr111fs frameshift NM_001127444.2:c.332_333del NP_001120916.1:p.Thr111fs frameshift NM_001289908.1:c.332_333del NP_001276837.1:p.Thr111fs frameshift NM_001289909.1:c.332_333del NP_001276838.1:p.Thr111fs frameshift NM_001289911.2:c.104_105del NP_001276840.1:p.Thr35fs frameshift NM_001371074.1:c.332_333del NP_001358003.1:p.Thr111fs frameshift NM_001371075.1:c.332_333del NP_001358004.1:p.Thr111fs frameshift NM_001371077.1:c.332_333del NP_001358006.1:p.Thr111fs frameshift NM_001371078.1:c.332_333del NP_001358007.1:p.Thr111fs frameshift NM_001371079.1:c.230_231del NP_001358008.1:p.Thr77fs frameshift NM_001371080.1:c.-136CA[1] 5 prime UTR NM_001371081.1:c.-153CA[1] 5 prime UTR NR_110501.1:n.509CA[1] non-coding transcript variant NC_000007.14:g.80661111CA[1] NC_000007.13:g.80290427CA[1] NG_008192.1:g.63924CA[1] - Protein change
- T35fs, T111fs, T77fs
- Other names
- -
- Canonical SPDI
- NC_000007.14:80661109:ACACA:ACA
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00379 (ACA)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| CD36 | - | - |
GRCh38 GRCh37 |
248 | 271 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Apr 22, 2021 | RCV000490431.8 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Oct 26, 2021 | RCV002503831.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
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Pathogenic
(Mar 18, 2016)
|
criteria provided, single submitter
Method: reference population
|
Platelet-type bleeding disorder 10
Affected status: unknown
Allele origin:
germline
|
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center
Accession: SCV000267242.1
First in ClinVar: May 25, 2017 Last updated: May 25, 2017 |
Number of individuals with the variant: 1
Age: 40-69 years
Ethnicity/Population group: East Asian
Geographic origin: South Korean
|
|
|
Pathogenic
(Oct 05, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Platelet-type bleeding disorder 10
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000915227.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
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 … (more)
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. (less)
|
|
|
Pathogenic
(Apr 22, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Platelet-type bleeding disorder 10
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556855.2
First in ClinVar: Aug 08, 2022 Last updated: Dec 17, 2022 |
|
|
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Pathogenic
(Oct 26, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Platelet-type bleeding disorder 10
Coronary heart disease, susceptibility to, 7 Malaria, susceptibility to
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002804913.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
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Pathogenic
(Jan 06, 2020)
|
no assertion criteria provided
Method: curation
|
Platelet glycoprotein IV deficiency
Affected status: unknown
Allele origin:
germline
|
Reproductive Health Research and Development, BGI Genomics
Accession: SCV001142371.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
Comment:
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 … (more)
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. (less)
|
Comment:
Comment:
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.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
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.
Comment:
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.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Diverse CD36 expression among Japanese population: defective CD36 mutations cause platelet and monocyte CD36 reductions in not only deficient but also normal phenotype subjects. | Masuda Y | Thrombosis research | 2015 | PMID: 25798958 |
| Incidence and molecular basis of CD36 deficiency in Shanghai population. | Li R | Transfusion | 2015 | PMID: 25330908 |
| Studies on CD36 deficiency in South China: Two cases demonstrating the clinical impact of anti-CD36 antibodies. | Xu X | Thrombosis and haemostasis | 2013 | PMID: 23966019 |
| Polymorphisms of CD36 in Thai malaria patients. | Omi K | The Southeast Asian journal of tropical medicine and public health | 2002 | PMID: 12971464 |
| Human CD36 deficiency is associated with elevation in low-density lipoprotein-cholesterol. | Yanai H | American journal of medical genetics | 2000 | PMID: 10946357 |
| Identification of molecular defects in a subject with type I CD36 deficiency. | Kashiwagi H | Blood | 1994 | PMID: 7515716 |
Text-mined citations for rs572295823 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Apr 09, 2023
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.