The p.Arg2310Gly variant in PRPF8 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: PM2, PP3, PS3, PM1, PP1. 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.
ClinVar Genomic variation as it relates to human health
NM_006445.4(PRPF8):c.6928A>G (p.Arg2310Gly)
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.
(9)
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/Likely pathogenic
9
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_006445.4(PRPF8):c.6928A>G (p.Arg2310Gly)
Variation ID: 438226 Accession: VCV000438226.15
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17p13.3 17: 1650882 (GRCh38) [ NCBI UCSC ] 17: 1554176 (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 Sep 9, 2017 Dec 28, 2024 Oct 1, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_006445.4:c.6928A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_006436.3:p.Arg2310Gly missense NC_000017.11:g.1650882T>C NC_000017.10:g.1554176T>C NG_009118.1:g.39001A>G NG_033061.1:g.4217A>G - Protein change
- R2310G
- Other names
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NP_006436.3:p.(Arg2310Gly)
- Canonical SPDI
- NC_000017.11:1650881:T: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
Help
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
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. |
|||
| PRPF8 | - | - |
GRCh38 GRCh38 GRCh37 |
1387 | 1485 | |
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 (3) |
criteria provided, multiple submitters, no conflicts
|
Jul 24, 2023 | RCV000504770.6 | |
| Pathogenic (1) |
no assertion criteria provided
|
Aug 11, 2019 | RCV001257799.1 | |
| Pathogenic (2) |
criteria provided, single submitter
|
- | RCV001542603.3 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jul 17, 2023 | RCV001231748.5 | |
| Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Oct 1, 2023 | RCV003889914.2 |
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. |
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|---|---|---|---|---|---|
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Pathogenic
(Apr 01, 2021)
|
criteria provided, single submitter
Method: curation
|
Retinitis pigmentosa
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001950340.1
First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
Comment:
The p.Arg2310Gly variant in PRPF8 was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics … (more)
The p.Arg2310Gly variant in PRPF8 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: PM2, PP3, PS3, PM1, PP1. 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)
|
|
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Pathogenic
(Jul 24, 2023)
|
criteria provided, single submitter
Method: research
|
Retinitis pigmentosa
Affected status: yes
Allele origin:
germline
|
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel
Accession: SCV004030276.1
First in ClinVar: Sep 03, 2023 Last updated: Sep 03, 2023
Comment:
This variant was classified as Pathogenic based on ACMG criteria: PS4, PM2, PM5, PM1, PP3, PP2, PP5.
|
Comment:
Clinical significance based on ACMG v2.0
Number of individuals with the variant: 1
Sex: male
Geographic origin: Portugal
|
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Pathogenic
(Jul 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001404280.4
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2310 of the PRPF8 protein (p.Arg2310Gly). … (more)
This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2310 of the PRPF8 protein (p.Arg2310Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 11468273, 12714658, 16799052). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 438226). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PRPF8 protein function. Experimental studies have shown that this missense change affects PRPF8 function (PMID: 28515276). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
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Likely pathogenic
(Oct 01, 2023)
|
criteria provided, single submitter
Method: research
|
Retinal dystrophy
Affected status: yes
Allele origin:
germline
|
Dept Of Ophthalmology, Nagoya University
Accession: SCV004706136.1
First in ClinVar: Mar 10, 2024 Last updated: Mar 10, 2024 |
|
|
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Likely pathogenic
(Jan 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg
Accession: SCV005072607.1
First in ClinVar: Dec 28, 2024 Last updated: Dec 28, 2024 |
|
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Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 13
Affected status: yes
Allele origin:
germline
|
Juno Genomics, Hangzhou Juno Genomics, Inc
Accession: SCV005417696.1
First in ClinVar: Nov 30, 2024 Last updated: Nov 30, 2024 |
Comment:
PM2_Supporting+PS3+PP2+PS4_Moderate+PP4+PP1
|
|
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Likely 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: SCV000599196.1
First in ClinVar: Sep 09, 2017 Last updated: Sep 09, 2017 |
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: European
|
|
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Pathogenic
(Aug 11, 2019)
|
no assertion criteria provided
Method: literature only
|
Autosomal dominant Retinitis Pigmentosa
Affected status: yes
Allele origin:
germline
|
Faculty of Health Sciences, Beirut Arab University
Accession: SCV001434677.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Number of individuals with the variant: 1
Ethnicity/Population group: Arab
|
|
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Retinitis pigmentosa 13
Affected status: yes
Allele origin:
germline
|
Genomics England Pilot Project, Genomics England
Accession: SCV001760396.1
First in ClinVar: Jul 27, 2021 Last updated: Jul 27, 2021 |
|
Comment:
Comment:
Clinical significance based on ACMG v2.0
Comment:
This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2310 of the PRPF8 protein (p.Arg2310Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 11468273, 12714658, 16799052). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 438226). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PRPF8 protein function. Experimental studies have shown that this missense change affects PRPF8 function (PMID: 28515276). For these reasons, this variant has been classified as Pathogenic.
Comment:
PM2_Supporting+PS3+PP2+PS4_Moderate+PP4+PP1
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 p.Arg2310Gly variant in PRPF8 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: PM2, PP3, PS3, PM1, PP1. 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:
Clinical significance based on ACMG v2.0
Comment:
This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2310 of the PRPF8 protein (p.Arg2310Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 11468273, 12714658, 16799052). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 438226). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PRPF8 protein function. Experimental studies have shown that this missense change affects PRPF8 function (PMID: 28515276). For these reasons, this variant has been classified as Pathogenic.
Comment:
PM2_Supporting+PS3+PP2+PS4_Moderate+PP4+PP1
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| The first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesis. | Peter VG | PNAS nexus | 2023 | PMID: 36909829 |
| 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 |
| 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care - Preliminary Report. | 100,000 Genomes Project Pilot Investigators | The New England journal of medicine | 2021 | PMID: 34758253 |
| Molecular diagnosis based on comprehensive genetic testing in 800 Chinese families with non-syndromic inherited retinal dystrophies. | Liu X | Clinical & experimental ophthalmology | 2021 | PMID: 33090715 |
| Whole-genome sequencing of patients with rare diseases in a national health system. | Turro E | Nature | 2020 | PMID: 32581362 |
| PHENOTYPE-GUIDED GENETIC TESTING OF PEDIATRIC INHERITED RETINAL DISEASE IN THE UNITED ARAB EMIRATES. | Khan AO | Retina (Philadelphia, Pa.) | 2020 | PMID: 31725702 |
| Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients. | Koyanagi Y | Journal of medical genetics | 2019 | PMID: 31213501 |
| Toward the Mutational Landscape of Autosomal Dominant Retinitis Pigmentosa: A Comprehensive Analysis of 258 Spanish Families. | Martin-Merida I | Investigative ophthalmology & visual science | 2018 | PMID: 29847639 |
| Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP chaperones. | Malinová A | The Journal of cell biology | 2017 | PMID: 28515276 |
| 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 |
| PRPF mutations are associated with generalized defects in spliceosome formation and pre-mRNA splicing in patients with retinitis pigmentosa. | Tanackovic G | Human molecular genetics | 2011 | PMID: 21378395 |
| Prevalence of disease-causing mutations in families with autosomal dominant retinitis pigmentosa: a screen of known genes in 200 families. | Sullivan LS | Investigative ophthalmology & visual science | 2006 | PMID: 16799052 |
| Mutations in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 in Spanish families with autosomal dominant retinitis pigmentosa. | Martínez-Gimeno M | Investigative ophthalmology & visual science | 2003 | PMID: 12714658 |
| Mutations in the pre-mRNA splicing factor gene PRPC8 in autosomal dominant retinitis pigmentosa (RP13). | McKie AB | Human molecular genetics | 2001 | PMID: 11468273 |
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Text-mined citations for rs752997229 ...
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 Dec 28, 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.