Across a selection of the available literature, the CD36 c.268C>T (p.Pro90Ser) missense variant has been identified in at least 18 individuals with platelet glycoprotein IV deficiency, including in a homozygous state in at least 11 patients, in a compound heterozygous state in at least five patients, in one individual who was homozygous for the p.Pro90Ser variant and heterozygous for an insertion variant, and in one individual who carried the p.Pro90Ser variant, an insertion variant, and an additional missense variant (Kashiwagi H et al. 1993; Yanai H et al. 2000a; Hanawa et al. 2002). The p.Pro90Ser variant was reported in 0-3.5% of controls, but the allele frequencies were significantly higher in patients (24.5-28.6%) (Yanai et al. 2000a; Yanai et al. 2000b). The p.Pro90Ser variant is reported at a frequency of 0.04088 in the Japanese from Tokyo, Japan population of the 1000 Genomes Project. Functional studies showed that the p.Pro90Ser variant prevented maturation of the CD36 protein leading to degradation of the mutated precursor (Kashiwagi et al. 1995). The Pro90 residue is conserved in all members of the CD36 family. Based on the collective evidence, the p.Pro90Ser 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.268C>T (p.Pro90Ser)
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.
(6)
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.
Conflicting classifications of pathogenicity
Pathogenic(2); Likely pathogenic(1); Uncertain significance(1)
Pathogenic(2); Likely pathogenic(1); Uncertain significance(1)
6
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001001548.3(CD36):c.268C>T (p.Pro90Ser)
Variation ID: 13535 Accession: VCV000013535.15
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 7q21.11 7: 80656687 (GRCh38) [ NCBI UCSC ] 7: 80286003 (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 Apr 4, 2013 Feb 4, 2024 Aug 8, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001001548.3:c.268C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001001548.1:p.Pro90Ser missense NM_000072.3:c.268C>T NP_000063.2:p.Pro90Ser missense NM_001001547.3:c.268C>T NP_001001547.1:p.Pro90Ser missense NM_001127443.2:c.268C>T NP_001120915.1:p.Pro90Ser missense NM_001127444.2:c.268C>T NP_001120916.1:p.Pro90Ser missense NM_001289908.1:c.268C>T NP_001276837.1:p.Pro90Ser missense NM_001289909.1:c.268C>T NP_001276838.1:p.Pro90Ser missense NM_001289911.2:c.40C>T NP_001276840.1:p.Pro14Ser missense NM_001371074.1:c.268C>T NP_001358003.1:p.Pro90Ser missense NM_001371075.1:c.268C>T NP_001358004.1:p.Pro90Ser missense NM_001371077.1:c.268C>T NP_001358006.1:p.Pro90Ser missense NM_001371078.1:c.268C>T NP_001358007.1:p.Pro90Ser missense NM_001371079.1:c.166C>T NP_001358008.1:p.Pro56Ser missense NM_001371080.1:c.-184-4376C>T intron variant NM_001371081.1:c.-215C>T 5 prime UTR NR_110501.1:n.447C>T non-coding transcript variant NC_000007.14:g.80656687C>T NC_000007.13:g.80286003C>T NG_008192.1:g.59500C>T P16671:p.Pro90Ser - Protein change
- P90S, P14S, P56S
- Other names
- -
- Canonical SPDI
- NC_000007.14:80656686:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
-
0.00200 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD) 0.00011
Trans-Omics for Precision Medicine (TOPMed) 0.00012
The Genome Aggregation Database (gnomAD), exomes 0.00114
Exome Aggregation Consortium (ExAC) 0.00134
1000 Genomes Project 30x 0.00156
1000 Genomes Project 0.00200
- 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 |
246 | 269 | |
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/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Dec 20, 2019 | RCV000014490.28 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jun 9, 2020 | RCV000826087.6 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Aug 8, 2023 | RCV003330389.1 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Sep 26, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Platelet-type bleeding disorder 10
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000470083.3
First in ClinVar: Dec 06, 2016 Last updated: May 24, 2019 |
Comment:
Across a selection of the available literature, the CD36 c.268C>T (p.Pro90Ser) missense variant has been identified in at least 18 individuals with platelet glycoprotein IV … (more)
Across a selection of the available literature, the CD36 c.268C>T (p.Pro90Ser) missense variant has been identified in at least 18 individuals with platelet glycoprotein IV deficiency, including in a homozygous state in at least 11 patients, in a compound heterozygous state in at least five patients, in one individual who was homozygous for the p.Pro90Ser variant and heterozygous for an insertion variant, and in one individual who carried the p.Pro90Ser variant, an insertion variant, and an additional missense variant (Kashiwagi H et al. 1993; Yanai H et al. 2000a; Hanawa et al. 2002). The p.Pro90Ser variant was reported in 0-3.5% of controls, but the allele frequencies were significantly higher in patients (24.5-28.6%) (Yanai et al. 2000a; Yanai et al. 2000b). The p.Pro90Ser variant is reported at a frequency of 0.04088 in the Japanese from Tokyo, Japan population of the 1000 Genomes Project. Functional studies showed that the p.Pro90Ser variant prevented maturation of the CD36 protein leading to degradation of the mutated precursor (Kashiwagi et al. 1995). The Pro90 residue is conserved in all members of the CD36 family. Based on the collective evidence, the p.Pro90Ser 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)
|
|
|
Uncertain significance
(Aug 08, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004038409.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
Comment:
Variant summary: CD36 c.268C>T (p.Pro90Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Variant summary: CD36 c.268C>T (p.Pro90Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0011 in 250710 control chromosomes, predominantly at a frequency of 0.015 within the East Asian subpopulation in the gnomAD database, including 10 homozygotes. Due to the possibility of sub-clinical presentation and/or lack of phenotype information in this cohort, this frequency does not allow conclusions about variant significance. The c.268C>T has been reported in the literature as a homozygous genotype in multiple individuals affected with features of type 1 CD36 deficiency (example, Kashiwagi_1995, Hames_2014, Masuda_2015, Hanawa_2002). Some of these studies also reported the variant as a heterozygous genotype in individuals with type II CD36 deficiency. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported although one study has reported that this variant leads to CD36 deficiency via a defect in post-translational modification (Kashiwagi_1995). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. The following publications have been ascertained in the context of this evaluation (PMID: 24917573, 7533783, 25798958, 11019968, 11950861). All submitters classified the variant as pathogenic/likely pathogenic citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. (less)
|
|
|
Pathogenic
(Jun 09, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Inherited bleeding disorder, platelet-type
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000967583.2
First in ClinVar: Aug 26, 2019 Last updated: May 29, 2021 |
Comment:
The p.Pro90Ser variant in CD36, previously known as c.478C>T, has been reported in at least 17 homozygous, and 9 compound heterozygous individuals (predominantly individuals of … (more)
The p.Pro90Ser variant in CD36, previously known as c.478C>T, has been reported in at least 17 homozygous, and 9 compound heterozygous individuals (predominantly individuals of Asian descent) with CD36 deficiency (type I or II, also known as platelet glycoprotein IV deficiency) (Kashiwagi 1995 PMID: 7533783, Yanai 2000a PMID: 11019968, Yanai 2000b PMID: 10946357, Kajihara 2001 PMID: 11718687, Hanawa 2002 PMID: 11950861, Hames 2014 PMID: 24917573, and Masuda 2015 PMID: 25798958). This variant also segregated with disease in 3 family members from 3 families (Yanai 2000a PMID: 11019968, Hanawa 2002 PMID: 11950861, Hames 2014 PMID: 24917573). In vitro functional provide support that this variant confers reduced expression in patient cell lines (Kashiwagi 1995 PMID: 7533783 and Masuda 2015 PMID: 25798958). This variant has also been reported in ClinVar (Variation ID 13535). This variant has been identified in 1.43% (284/19884) of East Asian chromosomes by gnomAD (http://gnomAD.broadinstitute.org). In summary, the p.Pro90Ser variant meets criteria to be classified as pathogenic for CD36 deficiency in an autosomal recessive manner based upon its occurrence in affected individuals and available functional studies. ACMG/AMP Criteria applied: PM3_Very Strong, PP1, PP3, PS3_Supporting. (less)
Number of individuals with the variant: 4
|
|
|
Likely pathogenic
(Dec 20, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Platelet-type bleeding disorder 10
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002025121.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(Apr 01, 2002)
|
no assertion criteria provided
Method: literature only
|
PLATELET GLYCOPROTEIN IV DEFICIENCY
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000034741.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In platelets from 4 of 5 Japanese patients with type II platelet glycoprotein IV deficiency (608404), Kashiwagi et al. (1993) demonstrated a 478C-T transition in … (more)
In platelets from 4 of 5 Japanese patients with type II platelet glycoprotein IV deficiency (608404), Kashiwagi et al. (1993) demonstrated a 478C-T transition in the CD36 gene, resulting in a pro90-to-ser (P90S) substitution. In platelets and monocytes from a patient with type I platelet glycoprotein IV deficiency, Kashiwagi et al. (1995) identified the P90S mutation. Expression assay using the C478 or T478 form of CD36 cDNA in transfected cells revealed that there was an 81-kD precursor form of CD36, and that the maturation of the 81-kD precursor form to the 88-kD mature form of CD36 was markedly impaired by the substitution. The mutated precursor form of CD36 was subsequently degraded in the cytoplasm. These results indicated that the C-T substitution at nucleotide 478 of the cDNA (which corresponds to nucleotide 12293 in exon 4 of the genomic sequence) directly leads to CD36 deficiency via defects in posttranslational modification, and that this substitution is the major defect underlying CD36 deficiency. Thus, type I individuals are presumably homozygous for P90S, whereas type II individuals are heterozygous. Yanai et al. (2000) found that the CD36 478T allele had a frequency of 3.5% among Japanese control chromosomes. In 6 patients with type I CD36 deficiency, Hanawa et al. (2002) identified homozygosity for the P90S mutation. Three additional type I patients were compound heterozygotes for the P90S mutation and another CD36 mutation. Clinical features of these patients included ischemic heart disease, hypertension, and congestive heart failure. (less)
|
|
|
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: SCV001142370.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
Comment:
NM_001001547.2:c.268C>T in the CD36 gene has an allele frequency of 0.014 in East Asian subpopulation in the gnomAD database. The c.268C>T (p.Pro90Ser) variant previously known … (more)
NM_001001547.2:c.268C>T in the CD36 gene has an allele frequency of 0.014 in East Asian subpopulation in the gnomAD database. The c.268C>T (p.Pro90Ser) variant previously known as c.478C>T, has been reported in 5 homozygous, and 3 compound heterozygous individuals (two with 1159A insertion and one with 1447C) with type I CD36 deficiency (PMID: 11950861). In vitro functional provide support that this variant confers reduced expression in patient cell lines (PMID: 25798958; 7533783). Taken together, we interprete this variant as Pathogenic/Likely pathogenic variant. ACMG/AMP Criteria applied: PM3_Strong; PS3; PP4. (less)
|
Comment:
Comment:
Variant summary: CD36 c.268C>T (p.Pro90Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0011 in 250710 control chromosomes, predominantly at a frequency of 0.015 within the East Asian subpopulation in the gnomAD database, including 10 homozygotes. Due to the possibility of sub-clinical presentation and/or lack of phenotype information in this cohort, this frequency does not allow conclusions about variant significance. The c.268C>T has been reported in the literature as a homozygous genotype in multiple individuals affected with features of type 1 CD36 deficiency (example, Kashiwagi_1995, Hames_2014, Masuda_2015, Hanawa_2002). Some of these studies also reported the variant as a heterozygous genotype in individuals with type II CD36 deficiency. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported although one study has reported that this variant leads to CD36 deficiency via a defect in post-translational modification (Kashiwagi_1995). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. The following publications have been ascertained in the context of this evaluation (PMID: 24917573, 7533783, 25798958, 11019968, 11950861). All submitters classified the variant as pathogenic/likely pathogenic citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Comment:
The p.Pro90Ser variant in CD36, previously known as c.478C>T, has been reported in at least 17 homozygous, and 9 compound heterozygous individuals (predominantly individuals of Asian descent) with CD36 deficiency (type I or II, also known as platelet glycoprotein IV deficiency) (Kashiwagi 1995 PMID: 7533783, Yanai 2000a PMID: 11019968, Yanai 2000b PMID: 10946357, Kajihara 2001 PMID: 11718687, Hanawa 2002 PMID: 11950861, Hames 2014 PMID: 24917573, and Masuda 2015 PMID: 25798958). This variant also segregated with disease in 3 family members from 3 families (Yanai 2000a PMID: 11019968, Hanawa 2002 PMID: 11950861, Hames 2014 PMID: 24917573). In vitro functional provide support that this variant confers reduced expression in patient cell lines (Kashiwagi 1995 PMID: 7533783 and Masuda 2015 PMID: 25798958). This variant has also been reported in ClinVar (Variation ID 13535). This variant has been identified in 1.43% (284/19884) of East Asian chromosomes by gnomAD (http://gnomAD.broadinstitute.org). In summary, the p.Pro90Ser variant meets criteria to be classified as pathogenic for CD36 deficiency in an autosomal recessive manner based upon its occurrence in affected individuals and available functional studies. ACMG/AMP Criteria applied: PM3_Very Strong, PP1, PP3, PS3_Supporting.
Comment:
NM_001001547.2:c.268C>T in the CD36 gene has an allele frequency of 0.014 in East Asian subpopulation in the gnomAD database. The c.268C>T (p.Pro90Ser) variant previously known as c.478C>T, has been reported in 5 homozygous, and 3 compound heterozygous individuals (two with 1159A insertion and one with 1447C) with type I CD36 deficiency (PMID: 11950861). In vitro functional provide support that this variant confers reduced expression in patient cell lines (PMID: 25798958; 7533783). Taken together, we interprete this variant as Pathogenic/Likely pathogenic variant. ACMG/AMP Criteria applied: PM3_Strong; PS3; PP4.
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:
Across a selection of the available literature, the CD36 c.268C>T (p.Pro90Ser) missense variant has been identified in at least 18 individuals with platelet glycoprotein IV deficiency, including in a homozygous state in at least 11 patients, in a compound heterozygous state in at least five patients, in one individual who was homozygous for the p.Pro90Ser variant and heterozygous for an insertion variant, and in one individual who carried the p.Pro90Ser variant, an insertion variant, and an additional missense variant (Kashiwagi H et al. 1993; Yanai H et al. 2000a; Hanawa et al. 2002). The p.Pro90Ser variant was reported in 0-3.5% of controls, but the allele frequencies were significantly higher in patients (24.5-28.6%) (Yanai et al. 2000a; Yanai et al. 2000b). The p.Pro90Ser variant is reported at a frequency of 0.04088 in the Japanese from Tokyo, Japan population of the 1000 Genomes Project. Functional studies showed that the p.Pro90Ser variant prevented maturation of the CD36 protein leading to degradation of the mutated precursor (Kashiwagi et al. 1995). The Pro90 residue is conserved in all members of the CD36 family. Based on the collective evidence, the p.Pro90Ser 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:
Variant summary: CD36 c.268C>T (p.Pro90Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0011 in 250710 control chromosomes, predominantly at a frequency of 0.015 within the East Asian subpopulation in the gnomAD database, including 10 homozygotes. Due to the possibility of sub-clinical presentation and/or lack of phenotype information in this cohort, this frequency does not allow conclusions about variant significance. The c.268C>T has been reported in the literature as a homozygous genotype in multiple individuals affected with features of type 1 CD36 deficiency (example, Kashiwagi_1995, Hames_2014, Masuda_2015, Hanawa_2002). Some of these studies also reported the variant as a heterozygous genotype in individuals with type II CD36 deficiency. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported although one study has reported that this variant leads to CD36 deficiency via a defect in post-translational modification (Kashiwagi_1995). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. The following publications have been ascertained in the context of this evaluation (PMID: 24917573, 7533783, 25798958, 11019968, 11950861). All submitters classified the variant as pathogenic/likely pathogenic citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Comment:
The p.Pro90Ser variant in CD36, previously known as c.478C>T, has been reported in at least 17 homozygous, and 9 compound heterozygous individuals (predominantly individuals of Asian descent) with CD36 deficiency (type I or II, also known as platelet glycoprotein IV deficiency) (Kashiwagi 1995 PMID: 7533783, Yanai 2000a PMID: 11019968, Yanai 2000b PMID: 10946357, Kajihara 2001 PMID: 11718687, Hanawa 2002 PMID: 11950861, Hames 2014 PMID: 24917573, and Masuda 2015 PMID: 25798958). This variant also segregated with disease in 3 family members from 3 families (Yanai 2000a PMID: 11019968, Hanawa 2002 PMID: 11950861, Hames 2014 PMID: 24917573). In vitro functional provide support that this variant confers reduced expression in patient cell lines (Kashiwagi 1995 PMID: 7533783 and Masuda 2015 PMID: 25798958). This variant has also been reported in ClinVar (Variation ID 13535). This variant has been identified in 1.43% (284/19884) of East Asian chromosomes by gnomAD (http://gnomAD.broadinstitute.org). In summary, the p.Pro90Ser variant meets criteria to be classified as pathogenic for CD36 deficiency in an autosomal recessive manner based upon its occurrence in affected individuals and available functional studies. ACMG/AMP Criteria applied: PM3_Very Strong, PP1, PP3, PS3_Supporting.
Comment:
NM_001001547.2:c.268C>T in the CD36 gene has an allele frequency of 0.014 in East Asian subpopulation in the gnomAD database. The c.268C>T (p.Pro90Ser) variant previously known as c.478C>T, has been reported in 5 homozygous, and 3 compound heterozygous individuals (two with 1159A insertion and one with 1447C) with type I CD36 deficiency (PMID: 11950861). In vitro functional provide support that this variant confers reduced expression in patient cell lines (PMID: 25798958; 7533783). Taken together, we interprete this variant as Pathogenic/Likely pathogenic variant. ACMG/AMP Criteria applied: PM3_Strong; PS3; PP4.
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 |
| Variants of CD36 gene and their association with CD36 protein expression in platelets. | Xu X | Blood transfusion = Trasfusione del sangue | 2014 | PMID: 24960640 |
| Free fatty acid uptake in humans with CD36 deficiency. | Hames KC | Diabetes | 2014 | PMID: 24917573 |
| A common haplotype at the CD36 locus is associated with high free fatty acid levels and increased cardiovascular risk in Caucasians. | Ma X | Human molecular genetics | 2004 | PMID: 15282206 |
| Identification of cryptic splice site, exon skipping, and novel point mutations in type I CD36 deficiency. | Hanawa H | Journal of medical genetics | 2002 | PMID: 11950861 |
| Association of the Pro90Ser CD36 mutation with elevated free fatty acid concentrations but not with insulin resistance syndrome in Japanese. | Kajihara S | Clinica chimica acta; international journal of clinical chemistry | 2001 | PMID: 11718687 |
| Phenotype-genotype correlation in CD36 deficiency types I and II. | Yanai H | Thrombosis and haemostasis | 2000 | PMID: 11019968 |
| Human CD36 deficiency is associated with elevation in low-density lipoprotein-cholesterol. | Yanai H | American journal of medical genetics | 2000 | PMID: 10946357 |
| Molecular basis of CD36 deficiency. Evidence that a 478C-->T substitution (proline90-->serine) in CD36 cDNA accounts for CD36 deficiency. | Kashiwagi H | The Journal of clinical investigation | 1995 | PMID: 7533783 |
| A novel polymorphism in glycoprotein IV (replacement of proline-90 by serine) predominates in subjects with platelet GPIV deficiency. | Kashiwagi H | Thrombosis and haemostasis | 1993 | PMID: 7686693 |
Text-mined citations for rs75326924 ...
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 Sep 29, 2024
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.