ClinVar Genomic variation as it relates to human health
NM_032119.4(ADGRV1):c.7006C>T (p.Arg2336Ter)
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_032119.4(ADGRV1):c.7006C>T (p.Arg2336Ter)
Variation ID: 143160 Accession: VCV000143160.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q14.3 5: 90692659 (GRCh38) [ NCBI UCSC ] 5: 89988476 (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 Aug 10, 2014 Feb 14, 2024 Jul 12, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_032119.4:c.7006C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_115495.3:p.Arg2336Ter nonsense NR_003149.2:n.7022C>T non-coding transcript variant NC_000005.10:g.90692659C>T NC_000005.9:g.89988476C>T NG_007083.2:g.168316C>T LRG_1095:g.168316C>T LRG_1095t1:c.7006C>T LRG_1095p1:p.Arg2336Ter - Protein change
- R2336*
- Other names
- -
- Canonical SPDI
- NC_000005.10:90692658: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
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00000
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
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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ADGRV1 | - | - |
GRCh38 GRCh37 |
6205 | 6258 |
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 (2) |
criteria provided, single submitter
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- | RCV000132687.6 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 23, 2016 | RCV000844604.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 12, 2022 | RCV001849954.3 |
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
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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
(-)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 2C
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV002820234.1
First in ClinVar: Jan 21, 2023 Last updated: Jan 21, 2023 |
Comment:
The stop gained p.R2336* in ADGRV1 (NM_032119.4) has been previously reported in 1 Chinese individual with Usher syndrome (Jiang et al, 2015). This variant is … (more)
The stop gained p.R2336* in ADGRV1 (NM_032119.4) has been previously reported in 1 Chinese individual with Usher syndrome (Jiang et al, 2015). This variant is predicted to cause loss of normal protein function through protein truncation. The p.R2336* variant is a loss of function variant in the gene ADGRV1, which is intolerant of Loss of Function variants. The amino acid change p.Arg2336Ter in ADGRV1 is predicted as conserved by GERP++ across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Hydrocephalus (present) , Anophthalmia (present) , Septo-optic dysplasia sequence (present) , Global developmental delay (present)
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Pathogenic
(Jul 12, 2022)
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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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Invitae
Accession: SCV002245919.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg2336*) in the ADGRV1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg2336*) in the ADGRV1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADGRV1 are known to be pathogenic (PMID: 19357117, 22135276, 22147658, 26226137, 30718709, 31047384, 32467589). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 143160). This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 26338283). (less)
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Pathogenic
(Nov 23, 2016)
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criteria provided, single submitter
Method: clinical testing
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Rare genetic deafness
(Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000731305.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
The p.Arg2336X variant in GPR98 has been previously reported in 1 Chinese indivi dual with Usher syndrome who was compound heterozygous for a second truncating … (more)
The p.Arg2336X variant in GPR98 has been previously reported in 1 Chinese indivi dual with Usher syndrome who was compound heterozygous for a second truncating v ariant in GPR98 (Jiang 2015). This variant has not been identified in large pop ulation studies. This nonsense variant leads to a premature termination codon at position 2336, which is predicted to lead to a truncated or absent protein. Los s of GPR98 function is an established disease mechanism in autosomal recessive U sher syndrome. In summary, this variant meets criteria to be classified as patho genic for autosomal recessive Usher syndrome based upon the predicted impact to the protein. (less)
Number of individuals with the variant: 1
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probable-pathogenic
(-)
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no assertion criteria provided
Method: not provided
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Usher syndrome, type 2C
Affected status: not provided
Allele origin:
not provided
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Department of Ophthalmology and Visual Sciences Kyoto University
Accession: SCV000172640.1
First in ClinVar: Aug 10, 2014 Last updated: Aug 10, 2014 |
Comment:
Converted during submission to Likely pathogenic.
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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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Frequency of Usher gene mutations in non-syndromic hearing loss: higher variability of the Usher phenotype. | Cesca F | Journal of human genetics | 2020 | PMID: 32467589 |
Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy. | Jespersgaard C | Scientific reports | 2019 | PMID: 30718709 |
Ultra-Widefield Fundus Autofluorescence Imaging of Patients with Retinitis Pigmentosa: A Standardized Grading System in Different Genotypes. | Hariri AH | Ophthalmology. Retina | 2018 | PMID: 31047384 |
Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort. | Bademci G | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26226137 |
Comprehensive molecular diagnosis of 67 Chinese Usher syndrome probands: high rate of ethnicity specific mutations in Chinese USH patients. | Jiang L | Orphanet journal of rare diseases | 2015 | PMID: 26338283 |
Non-USH2A mutations in USH2 patients. | Besnard T | Human mutation | 2012 | PMID: 22147658 |
Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study. | Le Quesne Stabej P | Journal of medical genetics | 2012 | PMID: 22135276 |
GPR98 mutations cause Usher syndrome type 2 in males. | Ebermann I | Journal of medical genetics | 2009 | PMID: 19357117 |
Text-mined citations for rs527236133 ...
HelpRecord last updated Apr 06, 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.