ClinVar Genomic variation as it relates to human health
NM_207352.4(CYP4V2):c.1091-2A>G
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
-
NM_207352.4(CYP4V2):c.1091-2A>G
Variation ID: 2191 Accession: VCV000002191.13
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 4q35.2 4: 186208863 (GRCh38) [ NCBI UCSC ] 4: 187130017 (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 May 3, 2013 Mar 10, 2024 Dec 10, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_207352.4:c.1091-2A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NC_000004.12:g.186208863A>G NC_000004.11:g.187130017A>G NG_007965.1:g.22344A>G NG_012095.2:g.4885A>G LRG_565:g.4885A>G - Protein change
- Other names
- IVS8AS, A-G, -2
- ISV8-2A>G
- Canonical SPDI
- NC_000004.12:186208862:A:G
-
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.
Exome Aggregation Consortium (ExAC) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00005
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. |
|||
CYP4V2 | - | - |
GRCh38 GRCh37 |
446 | 700 |
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 (4) |
criteria provided, multiple submitters, no conflicts
|
Apr 8, 2021 | RCV000002275.12 | |
Pathogenic (1) |
criteria provided, single submitter
|
Dec 10, 2023 | RCV001851576.5 | |
Likely pathogenic (1) |
criteria provided, single submitter
|
Oct 1, 2023 | RCV003887849.1 |
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. |
|
---|---|---|---|---|---|
Pathogenic
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Bietti crystalline corneoretinal dystrophy
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000448857.3
First in ClinVar: Dec 06, 2016 Last updated: May 24, 2019 |
Comment:
The CYP4V2 c.1091-2A>G variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. Across a … (more)
The CYP4V2 c.1091-2A>G variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. Across a selection of available literature, the c.1091-2A>G variant has been identified in 30 individuals with retinal atrophy, Bietti crystalline dystrophy, or retinitis pigmentosa, including in a homozygous state in five individuals and in a compound heterozygous state in 25 individuals. In addition, it was reported in a heterozygous state in five unaffected family members (Li et al. 2004; Xiao et al. 2011; Wang et al. 2012; Fu et al. 2013; Meng et al. 2014). The c.1091-2A>G variant was absent from 196 controls and is reported at a frequency of 0.00035 in the East Asian population of the Exome Aggregation Consortium. Based on the potential impact of splice acceptor variants and evidence from the literature, the c.1091-2A>G variant is classified as pathogenic for Bietti crystalline dystrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
|
|
Pathogenic
(Apr 08, 2021)
|
criteria provided, single submitter
Method: research
|
Bietti crystalline corneoretinal dystrophy
Affected status: yes
Allele origin:
germline
|
Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001573350.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Comment:
The CYP4V2 c.1091-2A>G variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we … (more)
The CYP4V2 c.1091-2A>G variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PM3. Based on this evidence we have classified this variant as Pathogenic. (less)
|
|
Pathogenic
(Dec 10, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002229249.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects an acceptor splice site in intron 8 of the CYP4V2 gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects an acceptor splice site in intron 8 of the CYP4V2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CYP4V2 are known to be pathogenic (PMID: 15042513, 25118264). This variant is present in population databases (rs199476183, gnomAD 0.06%). Disruption of this splice site has been observed in individual(s) with Bietti crystalline dystrophy and retinitis pigmentosa (PMID: 15042513). This variant is also known as IVS8-2A>G. ClinVar contains an entry for this variant (Variation ID: 2191). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
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: SCV004706595.1
First in ClinVar: Mar 10, 2024 Last updated: Mar 10, 2024 |
|
|
pathologic
(Apr 12, 2012)
|
no assertion criteria provided
Method: curation
|
Bietti Crystalline Dystrophy
Affected status: not provided
Allele origin:
not provided
|
GeneReviews
Accession: SCV000058224.2
First in ClinVar: Apr 04, 2013 Last updated: May 03, 2013 |
Comment:
Converted during submission to Pathogenic.
|
|
Pathogenic
(Jun 14, 2013)
|
no assertion criteria provided
Method: literature only
|
BIETTI CRYSTALLINE CORNEORETINAL DYSTROPHY
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000022433.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 29, 2015 |
Comment on evidence:
For discussion of the splice site mutation in the CYP4V2 gene (c.1091-2A-G, NM_207352.3) that was found in compound heterozygous state in patients with Bietti crystalline … (more)
For discussion of the splice site mutation in the CYP4V2 gene (c.1091-2A-G, NM_207352.3) that was found in compound heterozygous state in patients with Bietti crystalline corneoretinal dystrophy (BCD; 210370) by Lin et al. (2005), Li et al. (2004), Wang et al. (2012), and Fu et al. (2013), see 608614.0004 and 608614.0006. (less)
|
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 |
---|---|---|---|---|
Bietti Crystalline Dystrophy. | Adam MP | - | 2019 | PMID: 22497028 |
Identification of novel CYP4V2 gene mutations in 92 Chinese families with Bietti's crystalline corneoretinal dystrophy. | Meng XH | Molecular vision | 2014 | PMID: 25593508 |
Generation and characterization of a murine model of Bietti crystalline dystrophy. | Lockhart CM | Investigative ophthalmology & visual science | 2014 | PMID: 25118264 |
Next-generation sequencing-based molecular diagnosis of a Chinese patient cohort with autosomal recessive retinitis pigmentosa. | Fu Q | Investigative ophthalmology & visual science | 2013 | PMID: 23661369 |
Exome sequencing identifies compound heterozygous mutations in CYP4V2 in a pedigree with retinitis pigmentosa. | Wang Y | PloS one | 2012 | PMID: 22693542 |
Identification of CYP4V2 mutation in 21 families and overview of mutation spectrum in Bietti crystalline corneoretinal dystrophy. | Xiao X | Biochemical and biophysical research communications | 2011 | PMID: 21565171 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Recessive mutations in the CYP4V2 gene in East Asian and Middle Eastern patients with Bietti crystalline corneoretinal dystrophy. | Lin J | Journal of medical genetics | 2005 | PMID: 15937078 |
Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2. | Li A | American journal of human genetics | 2004 | PMID: 15042513 |
Text-mined citations for rs199476183 ...
HelpRecord last updated Jun 23, 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.