ClinVar Genomic variation as it relates to human health
NM_152443.3(RDH12):c.506G>A (p.Arg169Gln)
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_152443.3(RDH12):c.506G>A (p.Arg169Gln)
Variation ID: 623219 Accession: VCV000623219.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 14q24.1 14: 67727038 (GRCh38) [ NCBI UCSC ] 14: 68193755 (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 Mar 25, 2019 Feb 14, 2024 Dec 9, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_152443.3:c.506G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_689656.2:p.Arg169Gln missense NC_000014.9:g.67727038G>A NC_000014.8:g.68193755G>A NG_008321.1:g.30153G>A - Protein change
- R169Q
- Other names
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- Canonical SPDI
- NC_000014.9:67727037:G:A
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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.
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
- Links
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
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. |
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GPHN | Some evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
742 | 1857 | |
RDH12 | - | - |
GRCh38 GRCh37 |
3 | 611 |
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
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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/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Dec 9, 2023 | RCV000761341.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 13, 2018 | RCV001073859.2 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 17, 2022 | RCV001530599.3 |
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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Likely pathogenic
(Oct 13, 2016)
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criteria provided, single submitter
Method: clinical testing
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Leber congenital amaurosis 13
Affected status: yes
Allele origin:
germline
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Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota
Accession: SCV000891327.1
First in ClinVar: Mar 25, 2019 Last updated: Mar 25, 2019 |
Number of individuals with the variant: 1
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Pathogenic
(Jul 13, 2018)
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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: SCV001239423.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
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Likely pathogenic
(Jun 23, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001745482.1
First in ClinVar: Jul 07, 2021 Last updated: Jul 07, 2021 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis, which includes splice predictors and evolutionary conservation, … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 22065924, 25133751, 24705292, 32172635, 27535533, 28559085, 30134391) (less)
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Pathogenic
(Mar 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Leber congenital amaurosis 13
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002794784.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Dec 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital
Accession: SCV002818221.1
First in ClinVar: Jan 07, 2023 Last updated: Jan 07, 2023 |
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Pathogenic
(Dec 09, 2023)
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criteria provided, single submitter
Method: clinical testing
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Leber congenital amaurosis 13
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001213448.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 169 of the RDH12 protein (p.Arg169Gln). … (more)
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 169 of the RDH12 protein (p.Arg169Gln). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individuals with autosomal recessive Leber congenital amaurosis (PMID: 22065924, 25133751). ClinVar contains an entry for this variant (Variation ID: 623219). 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 RDH12 protein function with a positive predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Arg169 amino acid residue in RDH12. Other variant(s) that disrupt this residue have been observed in individuals with RDH12-related conditions (PMID: 22065924, 26047050), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Aug 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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Leber congenital amaurosis 13
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004208586.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Likely pathogenic
(Aug 01, 2019)
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no assertion criteria provided
Method: clinical testing
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Leber congenital amaurosis 13
Affected status: yes
Allele origin:
germline
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Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001146944.1
First in ClinVar: Jan 27, 2020 Last updated: Jan 27, 2020 |
Number of individuals with the variant: 1
Secondary finding: no
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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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Comprehensive Molecular Diagnosis of a Large Chinese Leber Congenital Amaurosis Cohort. | Wang H | Investigative ophthalmology & visual science | 2015 | PMID: 26047050 |
Mutation screening of retinal dystrophy patients by targeted capture from tagged pooled DNAs and next generation sequencing. | Watson CM | PloS one | 2014 | PMID: 25133751 |
RDH12 retinopathy: novel mutations and phenotypic description. | Mackay DS | Molecular vision | 2011 | PMID: 22065924 |
Text-mined citations for rs971610277 ...
HelpRecord last updated May 08, 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.