ClinVar Genomic variation as it relates to human health
NM_003719.5(PDE8B):c.895G>T (p.Glu299Ter)
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_003719.5(PDE8B):c.895G>T (p.Glu299Ter)
Variation ID: 3233764 Accession: VCV003233764.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q13.3 5: 77349437 (GRCh38) [ NCBI UCSC ] 5: 76645262 (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 May 8, 2024 Jul 7, 2024 Mar 26, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003719.5:c.895G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003710.1:p.Glu299Ter nonsense NM_001029851.4:c.876+4506G>T intron variant NM_001029852.4:c.895G>T NP_001025023.1:p.Glu299Ter nonsense NM_001029853.4:c.835G>T NP_001025024.1:p.Glu279Ter nonsense NM_001029854.4:c.877-1628G>T intron variant NM_001349748.3:c.892G>T NP_001336677.1:p.Glu298Ter nonsense NM_001349749.3:c.958G>T NP_001336678.1:p.Glu320Ter nonsense NM_001349750.3:c.655G>T NP_001336679.1:p.Glu219Ter nonsense NM_001349751.3:c.892G>T NP_001336680.1:p.Glu298Ter nonsense NM_001349752.3:c.589G>T NP_001336681.1:p.Glu197Ter nonsense NM_001349753.2:c.523G>T NP_001336682.1:p.Glu175Ter nonsense NM_001376062.1:c.592G>T NP_001362991.1:p.Glu198Ter nonsense NM_001376063.1:c.895G>T NP_001362992.1:p.Glu299Ter nonsense NM_001376064.1:c.895G>T NP_001362993.1:p.Glu299Ter nonsense NM_001376065.1:c.873+4506G>T intron variant NM_001376066.1:c.532G>T NP_001362995.1:p.Glu178Ter nonsense NM_001376067.1:c.523G>T NP_001362996.1:p.Glu175Ter nonsense NM_001376068.1:c.523G>T NP_001362997.1:p.Glu175Ter nonsense NM_001376069.1:c.634-1628G>T intron variant NM_001376070.1:c.574-1628G>T intron variant NM_001376071.1:c.571-1628G>T intron variant NM_001376072.1:c.592G>T NP_001363001.1:p.Glu198Ter nonsense NM_001376073.1:c.573+4506G>T intron variant NM_001376074.1:c.513+4506G>T intron variant NM_001376075.1:c.504+4506G>T intron variant NM_001414622.1:c.523G>T NP_001401551.1:p.Glu175Ter nonsense NM_001414623.1:c.523G>T NP_001401552.1:p.Glu175Ter nonsense NC_000005.10:g.77349437G>T NC_000005.9:g.76645262G>T NG_023364.2:g.174186G>T - Protein change
- E175*, E178*, E197*, E198*, E219*, E279*, E298*, E299*, E320*
- Other names
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- Canonical SPDI
- NC_000005.10:77349436:G:T
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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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- Links
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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PDE8B | - | - |
GRCh38 GRCh37 |
267 | 279 |
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
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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 (1) |
criteria provided, single submitter
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Mar 26, 2024 | RCV004527044.1 | |
PDE8B-Related Disorders
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Pathogenic (1) |
criteria provided, single submitter
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Mar 26, 2024 | RCV004579632.2 |
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
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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
(Mar 26, 2024)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis type 1
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV005039079.1
First in ClinVar: May 07, 2024 Last updated: May 07, 2024 |
Comment:
Variant summary: IDUA c.895G>T (p.Glu299X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: IDUA c.895G>T (p.Glu299X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 191150 control chromosomes. c.895G>T has been reported in the literature in individuals affected with Mucopolysaccharidosis Type 1. These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Mar 26, 2024)
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criteria provided, single submitter
Method: clinical testing
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PDE8B-Related Disorders
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV005062132.2
First in ClinVar: Jun 29, 2024 Last updated: Jul 07, 2024 |
Comment:
Variant summary: PDE8B c.895G>T (p.Glu299X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is … (more)
Variant summary: PDE8B c.895G>T (p.Glu299X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant was absent in 251194 control chromosomes (gnomAD). To our knowledge, no occurrence of c.895G>T in individuals affected with PDE8B-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic. (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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Jul 07, 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.