ClinVar Genomic variation as it relates to human health
NM_014489.4(PGAP2):c.713G>C (p.Arg238Pro)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_014489.4(PGAP2):c.713G>C (p.Arg238Pro)
Variation ID: 50503 Accession: VCV000050503.5
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p15.4 11: 3825024 (GRCh38) [ NCBI UCSC ] 11: 3846254 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Feb 9, 2015 Jul 16, 2023 Jul 8, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_014489.4:c.713G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_055304.1:p.Arg238Pro missense NM_001145438.2:c.689G>C NP_001138910.1:p.Arg230Pro missense NM_001256235.1:c.584G>C NP_001243164.1:p.Arg195Pro missense NM_001256236.1:c.884G>C NP_001243165.1:p.Arg295Pro missense NM_001256237.1:c.780G>C NP_001243166.1:p.Ser260= synonymous NM_001256238.1:c.603G>C NP_001243167.1:p.Ser201= synonymous NM_001256239.2:c.518G>C NP_001243168.1:p.Arg173Pro missense NM_001256240.2:c.530G>C NP_001243169.1:p.Arg177Pro missense NM_001283038.1:c.701G>C NP_001269967.1:p.Arg234Pro missense NM_001283039.1:c.654G>C NP_001269968.1:p.Ser218= synonymous NM_001283040.1:c.273G>C NP_001269969.1:p.Ser91= synonymous NM_001346397.2:c.683G>C NP_001333326.1:p.Arg228Pro missense NM_001346398.2:c.530G>C NP_001333327.1:p.Arg177Pro missense NM_001346399.2:c.540G>C NP_001333328.1:p.Ser180= synonymous NM_001346400.2:c.518G>C NP_001333329.1:p.Arg173Pro missense NM_001346401.2:c.528G>C NP_001333330.1:p.Ser176= synonymous NM_001346402.2:c.650G>C NP_001333331.1:p.Arg217Pro missense NM_001346403.1:c.792G>C NP_001333332.1:p.Ser264= synonymous NM_001346404.1:c.609G>C NP_001333333.1:p.Ser203= synonymous NM_001346405.1:c.530G>C NP_001333334.1:p.Arg177Pro missense NR_027016.3:n.457G>C non-coding transcript variant NR_027017.4:n.1074G>C non-coding transcript variant NR_027018.2:n.678G>C non-coding transcript variant NR_045923.2:n.472G>C non-coding transcript variant NR_045925.2:n.382G>C non-coding transcript variant NR_045926.2:n.394G>C non-coding transcript variant NR_045927.2:n.551G>C non-coding transcript variant NR_045929.2:n.573G>C non-coding transcript variant NR_104270.2:n.460G>C non-coding transcript variant NR_104271.2:n.720G>C non-coding transcript variant NR_104272.2:n.445G>C non-coding transcript variant NR_144427.2:n.545G>C non-coding transcript variant NR_144428.2:n.989G>C non-coding transcript variant NR_144429.2:n.741G>C non-coding transcript variant NR_144430.2:n.204G>C non-coding transcript variant NC_000011.10:g.3825024G>C NC_000011.9:g.3846254G>C NG_051812.1:g.32301G>C Q9UHJ9:p.Arg177Pro - Protein change
- R177P, R195P, R230P, R173P, R217P, R234P, R295P, R228P, R238P
- Other names
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- Canonical SPDI
- NC_000011.10:3825023:G:C
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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PGAP2 | - | - |
GRCh38 GRCh37 |
100 | 131 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jul 8, 2023 | RCV000043536.7 |
Submissions - Germline
Classification
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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
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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
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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
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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
(Jul 08, 2023)
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criteria provided, single submitter
Method: research
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Hyperphosphatasia with intellectual disability syndrome 3
Affected status: yes
Allele origin:
germline
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Institute of Experimental Medicine, Department of Genetics, Istanbul University
Accession: SCV004009699.1
First in ClinVar: Jul 16, 2023 Last updated: Jul 16, 2023 |
Number of individuals with the variant: 2
Sex: male
Ethnicity/Population group: Pakistani
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Hyperphosphatasia with intellectual disability syndrome 3
Affected status: yes
Allele origin:
unknown
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Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn
Accession: SCV000999351.1
First in ClinVar: Nov 30, 2019 Last updated: Nov 30, 2019 |
Number of individuals with the variant: 1
Clinical Features:
Delayed speech and language development (present) , Global developmental delay (present) , Elevated alkaline phosphatase (present) , Motor delay (present) , Absence seizures (present) , … (more)
Delayed speech and language development (present) , Global developmental delay (present) , Elevated alkaline phosphatase (present) , Motor delay (present) , Absence seizures (present) , Neonatal hypotonia (present) , Brain atrophy (present) (less)
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Pathogenic
(Apr 04, 2013)
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no assertion criteria provided
Method: literature only
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HYPERPHOSPHATASIA WITH IMPAIRED INTELLECTUAL DEVELOPMENT SYNDROME 3
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000071249.4
First in ClinVar: May 26, 2013 Last updated: Nov 13, 2022 |
Comment on evidence:
In affected members of a consanguineous Pakistani family (MR5) with autosomal recessive hyperphosphatasia with impaired intellectual development syndrome-3 (HPMRS3; 614207), originally reported by Rehman et … (more)
In affected members of a consanguineous Pakistani family (MR5) with autosomal recessive hyperphosphatasia with impaired intellectual development syndrome-3 (HPMRS3; 614207), originally reported by Rehman et al. (2011), Hansen et al. (2013) identified a homozygous c.530G-C transversion in the PGAP2 gene, resulting in an arg177-to-pro (R177P) substitution between transmembrane segments 3 and 4 in the Golgi lumen. The mutation, which was found by exome sequencing of the linked region on chromosome 11p15, was confirmed by Sanger sequencing and segregated with the disorder in the family. In vitro functional expression studies in CHO cells showed that the mutant protein was expressed but had significantly decreased activity compared to wildtype. Patient lymphoblastoid cells showed essentially normal expression of the GPI-anchored proteins DAF (125240) and CD59 (107271), supporting a hypomorphic effect of the R177P mutation. (less)
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Hypomorphic mutations in PGAP2, encoding a GPI-anchor-remodeling protein, cause autosomal-recessive intellectual disability. | Hansen L | American journal of human genetics | 2013 | PMID: 23561846 |
Autozygosity mapping of a large consanguineous Pakistani family reveals a novel non-syndromic autosomal recessive mental retardation locus on 11p15-tel. | Rehman Su | Neurogenetics | 2011 | PMID: 21643797 |
Text-mined citations for rs774843232 ...
HelpRecord last updated Aug 06, 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.