ClinVar Genomic variation as it relates to human health
NM_000283.4(PDE6B):c.892C>T (p.Gln298Ter)
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
-
NM_000283.4(PDE6B):c.892C>T (p.Gln298Ter)
Variation ID: 13103 Accession: VCV000013103.38
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 4p16.3 4: 654119 (GRCh38) [ NCBI UCSC ] 4: 647908 (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 Sep 14, 2015 Jun 17, 2024 Jan 19, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000283.4:c.892C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000274.3:p.Gln298Ter nonsense NM_001145291.2:c.892C>T NP_001138763.2:p.Gln298Ter nonsense NM_001145292.2:c.55C>T NP_001138764.2:p.Gln19Ter nonsense NM_001350154.3:c.55C>T NP_001337083.1:p.Gln19Ter nonsense NM_001350155.3:c.-149C>T 5 prime UTR NM_001379246.1:c.55C>T NP_001366175.1:p.Gln19Ter nonsense NM_001379247.1:c.55C>T NP_001366176.1:p.Gln19Ter nonsense NC_000004.12:g.654119C>T NC_000004.11:g.647908C>T NG_009839.1:g.33546C>T - Protein change
- Q298*, Q19*
- Other names
- -
- Canonical SPDI
- NC_000004.12:654118: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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00004
The Genome Aggregation Database (gnomAD) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00007
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. |
|||
PDE6B | - | - |
GRCh38 GRCh37 |
971 | 1259 | |
PDE6B-AS1 | - | - | - | GRCh38 | - | 200 |
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 (2) |
criteria provided, single submitter
|
Apr 8, 2021 | RCV000013982.23 | |
Pathogenic (2) |
criteria provided, single submitter
|
Apr 1, 2021 | RCV000504946.5 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jan 8, 2019 | RCV001074585.3 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Jan 19, 2024 | RCV000627220.30 |
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
(Apr 08, 2021)
|
criteria provided, single submitter
Method: research
|
Retinitis pigmentosa 40
Affected status: yes
Allele origin:
germline
|
Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001573377.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Comment:
The PDE6B c.892C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we … (more)
The PDE6B c.892C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PP1, PP3. Based on this evidence we have classified this variant as Pathogenic. (less)
|
|
Pathogenic
(Dec 31, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000748208.3
First in ClinVar: May 21, 2018 Last updated: Dec 15, 2018 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 7724547, 8394174, 22334370, 25525159, 25827439, 28981474, 28041643, 30998820, 32581362, 31589614) (less)
|
|
Pathogenic
(Apr 01, 2021)
|
criteria provided, single submitter
Method: curation
|
Retinitis pigmentosa
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001950316.1
First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
Comment:
The p.Gln298Ter variant in PDE6B was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics … (more)
The p.Gln298Ter variant in PDE6B was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PP1, PP3. Based on this evidence we have classified this variant as Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab. (less)
|
|
Pathogenic
(Aug 04, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000230892.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
Pathogenic
(Jan 08, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Retinal dystrophy
Affected status: yes
Allele origin:
germline
|
Blueprint Genetics
Accession: SCV001240176.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
|
|
|
Pathogenic
(Jan 19, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001588912.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln298*) in the PDE6B gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln298*) in the PDE6B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PDE6B are known to be pathogenic (PMID: 8394174, 8595886, 22334370). This variant is present in population databases (rs121918579, gnomAD 0.008%). This premature translational stop signal has been observed in individuals with autosomal recessive retinitis pigmentosa (PMID: 8394174, 28041643, 29472945). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13103). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Aug 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001246492.22
First in ClinVar: May 12, 2020 Last updated: Jun 17, 2024 |
Comment:
PDE6B: PVS1, PM2
Number of individuals with the variant: 5
|
|
Pathogenic
(Jun 01, 1993)
|
no assertion criteria provided
Method: literature only
|
RETINITIS PIGMENTOSA 40
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000034229.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 14, 2015 |
Comment on evidence:
In 2 sibs with autosomal recessive retinitis pigmentosa (RP40; 613801), McLaughlin et al. (1993) found compound heterozygosity for a gln298-to-ter (Q298X) mutation and an arg531-to-ter … (more)
In 2 sibs with autosomal recessive retinitis pigmentosa (RP40; 613801), McLaughlin et al. (1993) found compound heterozygosity for a gln298-to-ter (Q298X) mutation and an arg531-to-ter mutation (R531X; 180072.0002) in the PDE6B gene. The patients reported absent night vision since early childhood. Ophthalmoscopy showed attenuated retinal vessels and typical intraretinal bone-spicule pigment around the midperiphery. Rod and cone electroretinograms were abnormal. SSCP analysis was used in detecting mutations. The Q298X mutation resulted from a C-to-T transition at position 11638 in exon 5; the R531X mutation resulted from a C-to-T transition at position 18086 in exon 12. (less)
|
|
Pathogenic
(Jan 01, 2015)
|
no assertion criteria provided
Method: research
|
Retinitis pigmentosa
Affected status: yes
Allele origin:
unknown
|
NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV000599145.1
First in ClinVar: Sep 09, 2017 Last updated: Sep 09, 2017 |
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: European
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001922464.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001951594.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
click to load more click to collapse |
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 |
---|---|---|---|---|
The importance of automation in genetic diagnosis: Lessons from analyzing an inherited retinal degeneration cohort with the Mendelian Analysis Toolkit (MATK). | Zampaglione E | Genetics in medicine : official journal of the American College of Medical Genetics | 2022 | PMID: 34906470 |
An Update on Phosphodiesterase Mutations Underlying Genetic Etiology of Hearing Loss and Retinitis Pigmentosa. | Mittal R | Frontiers in genetics | 2018 | PMID: 29472945 |
The Genetic Basis of Pericentral Retinitis Pigmentosa-A Form of Mild Retinitis Pigmentosa. | Comander J | Genes | 2017 | PMID: 28981474 |
Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease. | Carss KJ | American journal of human genetics | 2017 | PMID: 28041643 |
Next-generation genetic testing for retinitis pigmentosa. | Neveling K | Human mutation | 2012 | PMID: 22334370 |
Mutations in the PDE6B gene in autosomal recessive retinitis pigmentosa. | Danciger M | Genomics | 1995 | PMID: 8595886 |
Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa. | McLaughlin ME | Nature genetics | 1993 | PMID: 8394174 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PDE6B | - | - | - | - |
Text-mined citations for rs121918579 ...
HelpRecord last updated Jun 23, 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.