ClinVar Genomic variation as it relates to human health
NM_000276.4(OCRL):c.2360_2361del (p.Val787fs)
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_000276.4(OCRL):c.2360_2361del (p.Val787fs)
Variation ID: 265392 Accession: VCV000265392.6
- Type and length
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Microsatellite, 2 bp
- Location
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Cytogenetic: Xq26.1 X: 129588902-129588903 (GRCh38) [ NCBI UCSC ] X: 128722879-128722880 (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 Oct 10, 2016 Feb 14, 2024 Jan 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000276.4:c.2360_2361del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000267.2:p.Val787fs frameshift NM_000276.3:c.2360_2361del NM_000276.3:c.2360_2361delTG NM_001318784.2:c.2363_2364del NP_001305713.1:p.Val788fs frameshift NM_001587.4:c.2336_2337del NP_001578.2:p.Val779fs frameshift NC_000023.11:g.129588902TG[1] NC_000023.10:g.128722879TG[1] NG_008638.1:g.53628TG[1] - Protein change
- V787fs, V779fs, V788fs
- Other names
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- Canonical SPDI
- NC_000023.11:129588901:TGTG:TG
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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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OCRL | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
720 | 912 |
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
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
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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 (1) |
criteria provided, single submitter
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Jun 17, 2016 | RCV000255112.1 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jan 10, 2023 | RCV002510570.5 |
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
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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
(Jun 17, 2016)
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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: SCV000322232.6
First in ClinVar: Oct 10, 2016 Last updated: Oct 10, 2016 |
Comment:
The c.2360_2361delTG variant in the OCRL gene has been reported previously as a pathogenic variant using alternate nomenclature (described as 2535–2536, 2536–2537, or 2537–2538delGT) in … (more)
The c.2360_2361delTG variant in the OCRL gene has been reported previously as a pathogenic variant using alternate nomenclature (described as 2535–2536, 2536–2537, or 2537–2538delGT) in association with Lowe syndrome (Lin et al., 1997; Hichri et al., 2011). The c.2360_2361delTG variant causes a frameshift starting with Valine 787, changes this amino acid to a Glycine residue, and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Val787GlyfsX2. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Functional studies on patient fibroblasts with this variant have shown reduced enzyme activity with no protein detectable by western blot (Lin et al., 1997). The c.2360_2361delTG variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret c.2360_2361delTG as a pathogenic variant. (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Lowe syndrome
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV002820267.1
First in ClinVar: Jan 21, 2023 Last updated: Jan 21, 2023 |
Comment:
The frameshift deletion p.V787Gfs*2 in OCRL (NM_000276.3) has been previously reported with an alternate nomenclature c.2538delGT in an affected patient. Functional studies confirmed absence of … (more)
The frameshift deletion p.V787Gfs*2 in OCRL (NM_000276.3) has been previously reported with an alternate nomenclature c.2538delGT in an affected patient. Functional studies confirmed absence of protein on western blot (Hichri et al, 2011). The variant has been submitted to ClinVar as Pathogenic. The p.V787Gfs*2 variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been reported to be disease causing previously (less)
Clinical Features:
Global developmental delay (present) , Hypotonia (present)
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Pathogenic
(Jan 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Lowe syndrome
Affected status: unknown
Allele origin:
germline
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Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV003839078.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
Comment:
This OCRL variant (rs886039519) is absent from a large population dataset and has an entry in ClinVar. It has been reported previously in individuals with … (more)
This OCRL variant (rs886039519) is absent from a large population dataset and has an entry in ClinVar. It has been reported previously in individuals with Lowe syndrome. This frameshift variant in exon 22 of 24 results in a premature termination codon (PTC) likely leading to nonsense-mediated decay and lack of protein production. Experimental studies using patient fibroblasts with this variant have shown reduced enzyme activity and no detectable protein by western blot. We consider c.2360_2361del (p.Val787fs) to be pathogenic. (less)
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Pathogenic
(Apr 07, 2022)
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criteria provided, single submitter
Method: clinical testing
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Lowe syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003445774.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This premature translational stop signal has been observed in individual(s) with OCRL-related conditions (PMID: 9199559). For these reasons, this variant has been classified as Pathogenic. … (more)
This premature translational stop signal has been observed in individual(s) with OCRL-related conditions (PMID: 9199559). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 265392). This variant is also known as 2535-2536, 2536-2537, or 2537-2538delGT. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val787Glyfs*2) in the OCRL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OCRL are known to be pathogenic (PMID: 19390221, 21031565, 22381590). (less)
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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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Inositol 5-phosphatases: insights from the Lowe syndrome protein OCRL. | Pirruccello M | Trends in biochemical sciences | 2012 | PMID: 22381590 |
From Lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes. | Hichri H | Human mutation | 2011 | PMID: 21031565 |
OCRL1 mutations in Dent 2 patients suggest a mechanism for phenotypic variability. | Shrimpton AE | Nephron. Physiology | 2009 | PMID: 19390221 |
Spectrum of mutations in the OCRL1 gene in the Lowe oculocerebrorenal syndrome. | Lin T | American journal of human genetics | 1997 | PMID: 9199559 |
Text-mined citations for rs886039519 ...
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.