The RPGR c.3092del variant was identified in an individual with retinitis pigmentosa with a presumed X-linked inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PP3, PM2, PP1-M. Based on this evidence we have classified this variant as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_001034853.2(RPGR):c.3092del (p.Glu1031fs)
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.
(10)
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.
Pathogenic
10
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001034853.2(RPGR):c.3092del (p.Glu1031fs)
Variation ID: 866381 Accession: VCV000866381.40
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: Xp11.4 X: 38285907 (GRCh38) [ NCBI UCSC ] X: 38145160 (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 18, 2020 Oct 20, 2024 Apr 1, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001034853.2:c.3092del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001030025.1:p.Glu1031fs frameshift NM_000328.3:c.1905+1187del intron variant NM_001367245.1:c.1902+1187del intron variant NM_001367246.1:c.1719+1187del intron variant NM_001367247.1:c.1572+5052del intron variant NM_001367248.1:c.1602+5052del intron variant NM_001367249.1:c.1569+5052del intron variant NM_001367250.1:c.1569+5052del intron variant NM_001367251.1:c.1386+5052del intron variant NC_000023.11:g.38285907del NC_000023.10:g.38145160del NG_009553.1:g.46629del - Protein change
- E1031fs
- Other names
- -
- Canonical SPDI
- NC_000023.11:38285906:T:
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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.
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Trans-Omics for Precision Medicine (TOPMed) 0.00001
- 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. |
|||
| RPGR | - | - |
GRCh38 GRCh37 |
1512 | 1685 | |
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 (1) |
criteria provided, single submitter
|
Jun 29, 2019 | RCV001074314.4 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Apr 1, 2024 | RCV001090908.29 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Jan 3, 2022 | RCV001251566.5 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Feb 15, 2022 | RCV002290587.4 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Oct 5, 2023 | RCV002557909.5 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Apr 1, 2021 | RCV001724237.5 |
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. |
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|---|---|---|---|---|---|
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Pathogenic
(Jun 29, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Retinal dystrophy
Affected status: yes
Allele origin:
germline
|
Blueprint Genetics
Accession: SCV001239887.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
|
|
|
|
Pathogenic
(Apr 08, 2021)
|
criteria provided, single submitter
Method: research
|
Retinitis pigmentosa 3
Affected status: yes
Allele origin:
germline
|
Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001573326.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Comment:
The RPGR c.3092del variant was identified in an individual with retinitis pigmentosa with a presumed X-linked inheritance pattern. Through a review of available evidence we … (more)
The RPGR c.3092del variant was identified in an individual with retinitis pigmentosa with a presumed X-linked inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PP3, PM2, PP1-M. Based on this evidence we have classified this variant as Pathogenic. (less)
|
|
|
Pathogenic
(Apr 01, 2021)
|
criteria provided, single submitter
Method: curation
|
Retinitis pigmentosa
(X-linked inheritance)
Affected status: yes
Allele origin:
germline
|
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001950366.1
First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
Comment:
The p.Glu1031GlyfsTer58 variant in RPGR was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics … (more)
The p.Glu1031GlyfsTer58 variant in RPGR 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, PP3, PM2, PP1-M. 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
(Jan 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Retinitis pigmentosa 3
Affected status: yes
Allele origin:
germline
|
3billion
Accession: SCV002058896.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported … (more)
Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). The variant has been reported at least twice as pathogenic/likely pathogenic (ClinVar ID: VCV000866381, PMID: 31645972). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Visual impairment (present) , Abnormal retinal morphology (present)
|
|
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Pathogenic
(Feb 15, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
X-linked cone-rod dystrophy 1
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002580631.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PM2_SUP, PP1
|
Number of individuals with the variant: 1
Sex: male
|
|
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Pathogenic
(Nov 13, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV002759696.1
First in ClinVar: Dec 11, 2022 Last updated: Dec 11, 2022 |
|
|
|
Pathogenic
(Sep 11, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV003840811.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation, as the last 122 amino acids are replaced with 57 different amino acids, and other loss-of-function variants … (more)
Frameshift variant predicted to result in protein truncation, as the last 122 amino acids are replaced with 57 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); Also known as ORF15+1339delA; This variant is associated with the following publications: (PMID: 33355362, 30567410, 24077912, 31804667, 31645972, 32795431, 12657579, 18332319, 18552978, 27798110) (less)
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Pathogenic
(Oct 05, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Primary ciliary dyskinesia
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003445110.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu1031Glyfs*58) in the RPGR (ORF15) gene. While this is not anticipated to result in nonsense mediated … (more)
This sequence change creates a premature translational stop signal (p.Glu1031Glyfs*58) in the RPGR (ORF15) gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 122 amino acid(s) of the RPGR (ORF15) protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 12657579, 18332319, 31804667). This variant is also known as ORF15+1339delA. ClinVar contains an entry for this variant (Variation ID: 866381). This variant disrupts a region of the RPGR (ORF15) protein in which other variant(s) (p.Leu1130Lysfs*13) have been determined to be pathogenic (PMID: 22264887; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Apr 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001246679.26
First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024 |
Comment:
RPGR: PVS1:Strong, PM1, PM2, PS4:Moderate
Number of individuals with the variant: 4
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Retinitis pigmentosa 3
Affected status: yes
Allele origin:
germline
|
Blueprint Genetics
Accession: SCV001427346.1
First in ClinVar: Aug 13, 2020 Last updated: Aug 13, 2020 |
|
Comment:
Comment:
The p.Glu1031GlyfsTer58 variant in RPGR 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, PP3, PM2, PP1-M. 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.
Comment:
Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). The variant has been reported at least twice as pathogenic/likely pathogenic (ClinVar ID: VCV000866381, PMID: 31645972). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Comment:
Frameshift variant predicted to result in protein truncation, as the last 122 amino acids are replaced with 57 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); Also known as ORF15+1339delA; This variant is associated with the following publications: (PMID: 33355362, 30567410, 24077912, 31804667, 31645972, 32795431, 12657579, 18332319, 18552978, 27798110)
Comment:
This sequence change creates a premature translational stop signal (p.Glu1031Glyfs*58) in the RPGR (ORF15) gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 122 amino acid(s) of the RPGR (ORF15) protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 12657579, 18332319, 31804667). This variant is also known as ORF15+1339delA. ClinVar contains an entry for this variant (Variation ID: 866381). This variant disrupts a region of the RPGR (ORF15) protein in which other variant(s) (p.Leu1130Lysfs*13) have been determined to be pathogenic (PMID: 22264887; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Comment:
RPGR: PVS1:Strong, PM1, PM2, PS4:Moderate
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:
The RPGR c.3092del variant was identified in an individual with retinitis pigmentosa with a presumed X-linked inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PP3, PM2, PP1-M. Based on this evidence we have classified this variant as Pathogenic.
Comment:
The p.Glu1031GlyfsTer58 variant in RPGR 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, PP3, PM2, PP1-M. 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.
Comment:
Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). The variant has been reported at least twice as pathogenic/likely pathogenic (ClinVar ID: VCV000866381, PMID: 31645972). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Comment:
Frameshift variant predicted to result in protein truncation, as the last 122 amino acids are replaced with 57 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); Also known as ORF15+1339delA; This variant is associated with the following publications: (PMID: 33355362, 30567410, 24077912, 31804667, 31645972, 32795431, 12657579, 18332319, 18552978, 27798110)
Comment:
This sequence change creates a premature translational stop signal (p.Glu1031Glyfs*58) in the RPGR (ORF15) gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 122 amino acid(s) of the RPGR (ORF15) protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 12657579, 18332319, 31804667). This variant is also known as ORF15+1339delA. ClinVar contains an entry for this variant (Variation ID: 866381). This variant disrupts a region of the RPGR (ORF15) protein in which other variant(s) (p.Leu1130Lysfs*13) have been determined to be pathogenic (PMID: 22264887; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Comment:
RPGR: PVS1:Strong, PM1, PM2, PS4:Moderate
Citations for germline classification of this variant
Help| Title | 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 |
| Reanalysis of Association of Pro50Leu Substitution in Guanylate Cyclase Activating Protein-1 With Dominant Retinal Dystrophy. | Mahroo OA | JAMA ophthalmology | 2020 | PMID: 31804667 |
| Clinical and genetic characteristics of 14 patients from 13 Japanese families with RPGR-associated retinal disorder: report of eight novel variants. | Mawatari G | Human genome variation | 2019 | PMID: 31645972 |
| Clinical course, genetic etiology, and visual outcome in cone and cone-rod dystrophy. | Thiadens AA | Ophthalmology | 2012 | PMID: 22264887 |
| Discordant phenotypes in fraternal twins having an identical mutation in exon ORF15 of the RPGR gene. | Walia S | Archives of ophthalmology (Chicago, Ill. : 1960) | 2008 | PMID: 18332319 |
| X-linked retinitis pigmentosa: RPGR mutations in most families with definite X linkage and clustering of mutations in a short sequence stretch of exon ORF15. | Bader I | Investigative ophthalmology & visual science | 2003 | PMID: 12657579 |
Text-mined citations for rs1186795749 ...
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 Nov 03, 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.