ClinVar Genomic variation as it relates to human health
NM_000283.4(PDE6B):c.2193+1G>A
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.2193+1G>A
Variation ID: 167440 Accession: VCV000167440.26
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 4p16.3 4: 664945 (GRCh38) [ NCBI UCSC ] 4: 658734 (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 8, 2017 Mar 16, 2024 Jan 8, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000283.4:c.2193+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001145291.2:c.2193+1G>A splice donor NM_001145292.2:c.1356+1G>A splice donor NM_001350154.3:c.1356+1G>A splice donor NM_001350155.3:c.1038+1G>A splice donor NM_001379246.1:c.1356+1G>A splice donor NM_001379247.1:c.1356+1G>A splice donor NC_000004.12:g.664945G>A NC_000004.11:g.658734G>A NG_009839.1:g.44372G>A NG_009839.2:g.44374G>A - Protein change
- Other names
- -
- Canonical SPDI
- NC_000004.12:664944:G:A
-
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.
Trans-Omics for Precision Medicine (TOPMed) 0.00003
Exome Aggregation Consortium (ExAC) 0.00008
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 |
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 | RCV000153667.12 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Apr 1, 2021 | RCV000216602.9 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Jan 8, 2024 | RCV000723948.15 | |
PDE6B-related disorder
|
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Oct 20, 2023 | RCV003387510.2 |
Pathogenic (1) |
criteria provided, single submitter
|
Aug 16, 2018 | RCV001073971.3 | |
Pathogenic (1) |
criteria provided, single submitter
|
Sep 7, 2021 | RCV002498731.2 |
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
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
(Mar 11, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Retinitis pigmentosa
(Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000271435.3
First in ClinVar: May 29, 2016 Last updated: Jul 22, 2019 |
Comment:
The c.2193+1G>A variant in PDE6B has previously been reported in one individual with retinal dystrophy (Wang 2014) and in one individual with retinitis pigmento sa … (more)
The c.2193+1G>A variant in PDE6B has previously been reported in one individual with retinal dystrophy (Wang 2014) and in one individual with retinitis pigmento sa and was found to segregate with disease in an affected sibling (McLaughlin 19 95). All of these individuals were compound heterozygous. This variant has also been identified in 0.01% (9/66178) of European chromosomes by the Exome Aggregat ion Consortium (http://exac.broadinstitute.org/). Although this variant has bee n seen in the general population, its frequency is low enough to be consistent w ith a recessive carrier frequency. This variant occurs in the invariant region ( +/- 1/2) of the splice consensus sequence and is predicted to cause altered spli cing leading to an abnormal or absent protein. Complete loss of PDE6B function i s an established disease mechanism in retinitis pigmentosa. In summary, this var iant meets our criteria to be classified as pathogenic for retinitis pigmentosa in an autosomal recessive manner (www.partners.org/personalizedmedicine/lmm). (less)
Number of individuals with the variant: 1
|
|
Pathogenic
(Aug 16, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Retinal dystrophy
Affected status: yes
Allele origin:
germline
|
Blueprint Genetics
Accession: SCV001239537.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
|
|
|
Pathogenic
(Sep 07, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital stationary night blindness autosomal dominant 2
Retinitis pigmentosa 40
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002809814.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Pathogenic
(Aug 21, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
PDE6B-related disorder
Affected status: yes
Allele origin:
germline
|
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV004099052.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
PM3_Strong, PP1, PP3_Strong, PM2
|
|
Pathogenic
(Jan 08, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001213695.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects a donor splice site in intron 18 of the PDE6B gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects a donor splice site in intron 18 of the PDE6B gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PDE6B are known to be pathogenic (PMID: 8394174, 8595886, 22334370). This variant is present in population databases (rs727504075, gnomAD 0.01%). Disruption of this splice site has been observed in individuals with autosomal recessive retinitis pigmentosa or retinal dystrophy (PMID: 7724547, 25097241, 28041643, 28224992). It has also been observed to segregate with disease in related individuals. This variant is also known as a G>A transition at position 22624. ClinVar contains an entry for this variant (Variation ID: 167440). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Oct 20, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
PDE6B-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004719596.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The PDE6B c.2193+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been documented causative for autosomal … (more)
The PDE6B c.2193+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been documented causative for autosomal recessive retinitis pigmentosa (arRP) (McLaughlin et al. 1995 PubMed ID: 7724547; Wang et al. 2014. PubMed ID: 25097241). This variant is reported in 0.015% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-658734-G-A). Variants that disrupt the consensus splice donor site in PDE6B are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
|
|
Pathogenic
(Oct 08, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000203224.7
First in ClinVar: Jan 31, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 3
Sex: mixed
|
|
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: SCV001573522.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Comment:
The PDE6B c.2193+1G>A 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.2193+1G>A 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
(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: SCV001950318.1
First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
Comment:
The c.2193+1G>A 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 c.2193+1G>A 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
(Apr 01, 2018)
|
no assertion criteria provided
Method: research
|
Retinitis pigmentosa
Affected status: yes
Allele origin:
unknown
|
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Study: VeluxRD
Accession: SCV000926634.2 First in ClinVar: Jul 22, 2019 Last updated: Sep 03, 2023 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001972444.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
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: SCV000599143.1
First in ClinVar: Sep 08, 2017 Last updated: Sep 08, 2017 |
Observation 1:
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: European
Observation 2:
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: European
|
|
Pathogenic
(Sep 01, 2016)
|
no assertion criteria provided
Method: clinical testing
|
Retinitis pigmentosa 40
Affected status: yes
Allele origin:
unknown
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Accession: SCV000804678.2
First in ClinVar: Sep 10, 2018 Last updated: Sep 10, 2018 |
Number of individuals with the variant: 1
|
|
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: SCV001920902.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 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: SCV001956724.1 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 |
Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy. | Jespersgaard C | Scientific reports | 2019 | PMID: 30718709 |
Diagnostic exome sequencing in 266 Dutch patients with visual impairment. | Haer-Wigman L | European journal of human genetics : EJHG | 2017 | PMID: 28224992 |
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 |
Dependable and efficient clinical utility of target capture-based deep sequencing in molecular diagnosis of retinitis pigmentosa. | Wang J | Investigative ophthalmology & visual science | 2014 | PMID: 25097241 |
Next-generation genetic testing for retinitis pigmentosa. | Neveling K | Human mutation | 2012 | PMID: 22334370 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Mutations in the PDE6B gene in autosomal recessive retinitis pigmentosa. | Danciger M | Genomics | 1995 | PMID: 8595886 |
Mutation spectrum of the gene encoding the beta subunit of rod phosphodiesterase among patients with autosomal recessive retinitis pigmentosa. | McLaughlin ME | Proceedings of the National Academy of Sciences of the United States of America | 1995 | PMID: 7724547 |
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 | - | - | - | - |
click to load more click to collapse |
Text-mined citations for rs727504075 ...
HelpRecord last updated Jun 30, 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.