ClinVar Genomic variation as it relates to human health
NM_006915.3(RP2):c.358C>T (p.Arg120Ter)
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_006915.3(RP2):c.358C>T (p.Arg120Ter)
Variation ID: 10551 Accession: VCV000010551.17
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xp11.3 X: 46853731 (GRCh38) [ NCBI UCSC ] X: 46713166 (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 Apr 4, 2013 Feb 14, 2024 Jun 29, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_006915.3:c.358C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_008846.2:p.Arg120Ter nonsense NC_000023.11:g.46853731C>T NC_000023.10:g.46713166C>T NG_009107.1:g.21820C>T - Protein change
- R120*
- Other names
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- Canonical SPDI
- NC_000023.11:46853730:C: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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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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RP2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
357 | 567 |
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 (3) |
criteria provided, multiple submitters, no conflicts
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Jun 3, 2021 | RCV000011297.8 | |
Pathogenic (2) |
criteria provided, single submitter
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Jul 11, 2019 | RCV000504994.4 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jun 29, 2023 | RCV001047806.9 | |
Pathogenic (3) |
criteria provided, single submitter
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Jan 24, 2023 | RCV000787701.5 |
Submissions - Germline
Classification
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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
(May 10, 2016)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 2
Affected status: yes
Allele origin:
germline
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Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota
Accession: SCV000890875.1
First in ClinVar: Mar 19, 2019 Last updated: Mar 19, 2019 |
Number of individuals with the variant: 1
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Pathogenic
(Jun 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 2
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556542.2
First in ClinVar: Aug 08, 2022 Last updated: Dec 17, 2022 |
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Pathogenic
(Jul 11, 2019)
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criteria provided, single submitter
Method: clinical testing
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV001241434.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447800.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Rod-cone dystrophy (present)
Sex: female
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Pathogenic
(Jan 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003801034.2
First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023 |
Comment:
Variant summary: RP2 c.358C>T (p.Arg120X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: RP2 c.358C>T (p.Arg120X) 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 are classified as pathogenic in ClinVar. The variant was absent in 183442 control chromosomes. c.358C>T has been reported in the literature in multiple individuals affected with Retinitis Pigmentosa, X-Linked with evidence of cosegregation with disease within families (Hardcastle_1999, Jin_2006, Sharon_2019). These data indicate that the variant is very likely to be associated with disease. Lymphoblastoid cells from male patients with the variant have been reported to show greatly reduced RP2 mRNA expression and absent RP2 protein (Grayson_2002). Eight submitters have provided clinical-significance assessments for this variant to ClinVar after 2014, and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jun 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001211787.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 10551). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 10551). This premature translational stop signal has been observed in individuals with X-linked retinitis pigmentosa (PMID: 10053026, 11262649, 25097241). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg120*) in the RP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RP2 are known to be pathogenic (PMID: 11992260, 20625056). (less)
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Pathogenic
(Jan 01, 2004)
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no assertion criteria provided
Method: literature only
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RETINITIS PIGMENTOSA 2
Affected status: not provided
Allele origin:
unknown
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OMIM
Accession: SCV000031525.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In affected members of 3 apparently unrelated families with X-linked retinitis pigmentosa (RP2; 312600), Hardcastle et al. (1999) identified a C-to-T transition at nucleotide 358 … (more)
In affected members of 3 apparently unrelated families with X-linked retinitis pigmentosa (RP2; 312600), Hardcastle et al. (1999) identified a C-to-T transition at nucleotide 358 in exon 2 of the RP2 gene, resulting in a change of codon 120 from CGA (arg) to TGA (stop) (R120X). The mutation resulted in truncation of the protein by 231 amino acids. Vorster et al. (2004) identified the R120X mutation in 2 affected half brothers; in the mother, an obligate carrier, no mutation could be detected in somatic cells, suggesting germline mosaicism. They speculated about the possibility of high mutability of a specific nucleotide. (less)
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Pathogenic
(Jan 01, 2015)
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no assertion criteria provided
Method: research
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Retinal dystrophy
Affected status: yes
Allele origin:
unknown
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NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV000598676.1
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
(Apr 01, 2018)
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no assertion criteria provided
Method: research
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Retinitis pigmentosa
Affected status: yes
Allele origin:
unknown
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Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Study: VeluxRD
Accession: SCV000926693.2 First in ClinVar: Jul 21, 2019 Last updated: Sep 03, 2023 |
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Pathogenic
(Jun 23, 2019)
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no assertion criteria provided
Method: research
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Retinitis pigmentosa
Affected status: yes
Allele origin:
inherited
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Sharon lab, Hadassah-Hebrew University Medical Center
Accession: SCV001161261.1
First in ClinVar: Feb 16, 2020 Last updated: Feb 16, 2020 |
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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
HelpTitle | Author | Journal | Year | Link |
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A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC). | Sharon D | Human mutation | 2020 | PMID: 31456290 |
Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy. | Jespersgaard C | Scientific reports | 2019 | PMID: 30718709 |
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 |
RP2 phenotype and pathogenetic correlations in X-linked retinitis pigmentosa. | Jayasundera T | Archives of ophthalmology (Chicago, Ill. : 1960) | 2010 | PMID: 20625056 |
Mutational analysis of RPGR and RP2 genes in Japanese patients with retinitis pigmentosa: identification of four mutations. | Jin ZB | Molecular vision | 2006 | PMID: 17093403 |
Arg120stop nonsense mutation in the RP2 gene: mutational hotspot and germ line mosaicism? | Vorster AA | Clinical genetics | 2004 | PMID: 15032968 |
A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of families with X-linked retinitis pigmentosa. | Breuer DK | American journal of human genetics | 2002 | PMID: 11992260 |
In vitro analysis of aminoglycoside therapy for the Arg120stop nonsense mutation in RP2 patients. | Grayson C | Journal of medical genetics | 2002 | PMID: 11826029 |
Phenotype associated with an R120X nonsense mutation in the RP2 gene in a Japanese family with X-linked retinitis pigmentosa. | Mashima Y | Ophthalmic genetics | 2001 | PMID: 11262649 |
Mutations in the RP2 gene cause disease in 10% of families with familial X-linked retinitis pigmentosa assessed in this study. | Hardcastle AJ | American journal of human genetics | 1999 | PMID: 10090907 |
Protein-truncation mutations in the RP2 gene in a North American cohort of families with X-linked retinitis pigmentosa. | Mears AJ | American journal of human genetics | 1999 | PMID: 10053026 |
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Text-mined citations for rs104894927 ...
HelpRecord last updated Oct 13, 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.