ClinVar Genomic variation as it relates to human health
NM_001384732.1(CPLANE1):c.8462-1G>C
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.
Pathogenic(1); Likely pathogenic(4); Uncertain significance(5)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001384732.1(CPLANE1):c.8462-1G>C
Variation ID: 197492 Accession: VCV000197492.42
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5p13.2 5: 37142481 (GRCh38) [ NCBI UCSC ] 5: 37142583 (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 Dec 6, 2016 May 12, 2024 Feb 23, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001384732.1:c.8462-1G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_023073.4:c.8300-1G>C splice acceptor NC_000005.10:g.37142481C>G NC_000005.9:g.37142583C>G NG_032772.2:g.111948G>C NG_032772.3:g.111895G>C - Protein change
- Other names
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- Canonical SPDI
- NC_000005.10:37142480:C:G
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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.
Exome Aggregation Consortium (ExAC) 0.00036
The Genome Aggregation Database (gnomAD), exomes 0.00038
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00046
The Genome Aggregation Database (gnomAD) 0.00060
Trans-Omics for Precision Medicine (TOPMed) 0.00060
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 | ||
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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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CPLANE1 | - | - |
GRCh38 GRCh37 |
2058 | 2169 |
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
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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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Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Dec 23, 2023 | RCV000178539.29 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Feb 23, 2024 | RCV000778764.10 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 16, 2024 | RCV001824663.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 31, 2022 | RCV002287379.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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- | RCV003457649.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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Dec 16, 2021 | RCV004020124.1 |
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
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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
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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Likely pathogenic
(Aug 12, 2016)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000230636.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 3
Sex: mixed
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Uncertain significance
(Oct 09, 2018)
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criteria provided, single submitter
Method: clinical testing
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Joubert syndrome 17
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000915131.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The C5orf42 c.8300-1G>C variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. A literature … (more)
The C5orf42 c.8300-1G>C variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. A literature search was performed for the gene and cDNA change. No publications were found based on this search. The variant is reported at a frequency of 0.000729 in the European (non-Finnish) population from the Genome Aggregation Database. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of splice acceptor variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for Joubert syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Uncertain significance
(-)
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criteria provided, single submitter
Method: not provided
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Orofaciodigital syndrome type 6
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, University Hospital of Duesseldorf
Accession: SCV004177249.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
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Uncertain significance
(Feb 23, 2024)
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criteria provided, single submitter
Method: clinical testing
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Joubert syndrome 17
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001524831.3
First in ClinVar: Mar 22, 2021 Last updated: Mar 10, 2024 |
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Uncertain significance
(Jan 16, 2024)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002074350.2
First in ClinVar: Feb 12, 2022 Last updated: Mar 30, 2024 |
Comment:
Variant summary: CPLANE1 c.8300-1G>C alters a conserved nucleotide located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered … (more)
Variant summary: CPLANE1 c.8300-1G>C alters a conserved nucleotide located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. One computational tool predicts an impact on normal splicing by abolishing a canonical 3' splice acceptor site. Three predict a non-informative impact on splicing based on lack of predictions for the wild-type and mutant sequences. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00076 in 1574996 control chromosomes in the gnomAD v4.0.0 database, including 1 homozygote. This frequency is not significantly higher than estimated for a pathogenic variant in CPLANE1 causing Joubert Syndrome And Related Disorders (0.00076 vs 0.0015), allowing no conclusion about variant significance. c.8300-1G>C has been reported in the literature as a heterozygous genotype with a likely pathogenic outcome in at-least one adult individual analyzed as part of a 3-year precision medicine study (example, Claire_2020). The exact clinical outcome, family history or the genotype of this occurrence is not clearly specified and the basis out the reported classification seems to be driven by the perceived translational outcome not bolstered by other supporting evidence as reported. Additionally, the variant has been reported in an individual with diabetic kidney disease (e.g., Lazaro-Guevara_2021). These reports do not provide unequivocal conclusions about association of the variant with Joubert Syndrome And Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31980526, 33774617). ClinVar contains an entry for this variant (Variation ID: 197492). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. (less)
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Uncertain significance
(Dec 16, 2021)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV004850631.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
Resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNA decay Based on insufficient or conflicting evidence, the clinical significance … (more)
Resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNA decay Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
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Pathogenic
(Jan 31, 2022)
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criteria provided, single submitter
Method: clinical testing
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see cases
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University Hospital Muenster
Accession: SCV002577956.1
First in ClinVar: Oct 08, 2022 Last updated: Oct 08, 2022 |
Comment:
ACMG categories: PVS1,PP3,PP5
Number of individuals with the variant: 1
Clinical Features:
Global developmental delay (present) , Hypotonia (present) , Abnormal facial shape (present)
Age: 0-9 years
Sex: female
Tissue: blood
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Likely pathogenic
(Jun 05, 2023)
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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: SCV000524825.6
First in ClinVar: Dec 06, 2016 Last updated: Jun 17, 2023 |
Comment:
Reported as a heterozygous variant in an unaffected parent in a study of children with developmental disorders (Fitzgerald et al., 2015); Reported in an individual … (more)
Reported as a heterozygous variant in an unaffected parent in a study of children with developmental disorders (Fitzgerald et al., 2015); Reported in an individual with diabetic kidney disease (Lazaro-Guevara et al., 2020); Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 31980526, 25533962) (less)
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Likely pathogenic
(Dec 23, 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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Invitae
Accession: SCV003011128.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
This sequence change affects an acceptor splice site in intron 42 of the CPLANE1 gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects an acceptor splice site in intron 42 of the CPLANE1 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 CPLANE1 are known to be pathogenic (PMID: 24178751, 26092869). This variant is present in population databases (rs151279194, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with CPLANE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 197492). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Likely pathogenic
(Jun 01, 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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247550.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Comment:
CPLANE1: PVS1:Strong, PM2
Number of individuals with the variant: 2
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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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Targeted Next-Generation Sequencing Identifies Pathogenic Variants in Diabetic Kidney Disease. | Lazaro-Guevara J | American journal of nephrology | 2021 | PMID: 33774617 |
Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging. | Hou YC | Proceedings of the National Academy of Sciences of the United States of America | 2020 | PMID: 31980526 |
Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity. | Bachmann-Gagescu R | Journal of medical genetics | 2015 | PMID: 26092869 |
C5orf42 is the major gene responsible for OFD syndrome type VI. | Lopez E | Human genetics | 2014 | PMID: 24178751 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=C5orf42 | - | - | - | - |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CPLANE1 | - | - | - | - |
Text-mined citations for rs151279194 ...
HelpRecord last updated May 12, 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.