ClinVar Genomic variation as it relates to human health
NM_001382391.1(CSPP1):c.2259_2260del (p.Glu755fs)
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_001382391.1(CSPP1):c.2259_2260del (p.Glu755fs)
Variation ID: 100667 Accession: VCV000100667.23
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 8q13.2 8: 67158463-67158464 (GRCh38) [ NCBI UCSC ] 8: 68070698-68070699 (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 13, 2015 Feb 20, 2024 Jul 17, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001382391.1:c.2259_2260del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001369320.1:p.Glu755fs frameshift NM_001291339.2:c.1209_1210del NP_001278268.1:p.Glu405fs frameshift NM_001363131.2:c.2178_2179del NP_001350060.1:p.Glu728fs frameshift NM_001363132.2:c.2064_2065del NP_001350061.1:p.Glu690fs frameshift NM_001363133.2:c.1983_1984del NP_001350062.1:p.Glu663fs frameshift NM_001364869.1:c.2325_2326del NP_001351798.1:p.Glu777fs frameshift NM_001364870.1:c.2145_2146del NP_001351799.1:p.Glu717fs frameshift NM_024790.6:c.2244_2245del NP_079066.5:p.Glu750fs frameshift NM_024790.6:c.2244_2245delAA NC_000008.11:g.67158464_67158465del NC_000008.10:g.68070699_68070700del NG_034100.1:g.99097_99098del - Protein change
- E717fs, E728fs, E750fs, E777fs, E690fs, E405fs, E663fs, E755fs
- Other names
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- Canonical SPDI
- NC_000008.11:67158462:AAA: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.
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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
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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CSPP1 | - | - |
GRCh38 GRCh37 |
917 | 1179 |
Conditions - Germline
Condition
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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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Pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Jul 17, 2023 | RCV000087067.21 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 5, 2023 | RCV001555416.7 |
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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Pathogenic
(Feb 23, 2015)
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criteria provided, single submitter
Method: research
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Joubert syndrome 21
Affected status: yes
Allele origin:
unknown
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UW Hindbrain Malformation Research Program, University of Washington
Additional submitter:
University of Washington Center for Mendelian Genomics, University of Washington
Accession: SCV000256397.1
First in ClinVar: Nov 09, 2015 Last updated: Nov 09, 2015 |
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Pathogenic
(Oct 24, 2018)
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criteria provided, single submitter
Method: clinical testing
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Joubert syndrome 21
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001367049.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PM2.
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Pathogenic
(May 11, 2018)
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criteria provided, single submitter
Method: clinical testing
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Joubert syndrome 21
Affected status: yes
Allele origin:
maternal
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Baylor Genetics
Accession: SCV001525746.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. The c.2244_2245delAA (p.E750Gfs*30) variant has been previously reported as disease causing in … (more)
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. The c.2244_2245delAA (p.E750Gfs*30) variant has been previously reported as disease causing in individuals with Joubert syndrome [PMID 24360807, 27894351, 24360808] (less)
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Pathogenic
(Dec 22, 2021)
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criteria provided, single submitter
Method: clinical testing
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Joubert syndrome 21
Affected status: yes
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV002061742.2
First in ClinVar: Jan 22, 2022 Last updated: Feb 11, 2022 |
Comment:
PVS1, PM2, PM3
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Pathogenic
(May 19, 2022)
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criteria provided, single submitter
Method: clinical testing
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Joubert syndrome 21
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002798572.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Jul 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: SCV001776834.4
First in ClinVar: Aug 13, 2021 Last updated: Jul 16, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 24360807, 24360808, 26092869, 27894351, 35183220) (less)
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Pathogenic
(Jul 17, 2023)
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criteria provided, single submitter
Method: clinical testing
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Joubert syndrome 21
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004029716.1
First in ClinVar: Aug 26, 2023 Last updated: Aug 26, 2023 |
Comment:
Variant summary: CSPP1 c.2244_2245delAA (p.Glu750GlyfsX30) results in a premature termination codon, predicted to cause an absence of the protein due to nonsense mediated decay, which … (more)
Variant summary: CSPP1 c.2244_2245delAA (p.Glu750GlyfsX30) results in a premature termination codon, predicted to cause an absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 9.2e-05 in 238258 control chromosomes. c.2244_2245delAA has been reported in the literature in individuals affected with ciliopathies such as Joubert Syndrome and Meckel-Gruber-like syndrome ((example, Tuz_2014, Fleming_2017). The following publications have been ascertained in the context of this evaluation (PMID: 29146704, 24360808). Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Feb 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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Joubert syndrome 21
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001415320.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu750Glyfs*30) in the CSPP1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Glu750Glyfs*30) in the CSPP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CSPP1 are known to be pathogenic (PMID: 24360807, 24360808). This variant is present in population databases (rs751779946, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with Joubert syndrome and Meckel syndrome (PMID: 24360807, 24360808, 27894351). ClinVar contains an entry for this variant (Variation ID: 100667). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 02, 2014)
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no assertion criteria provided
Method: literature only
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JOUBERT SYNDROME 21
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000119881.2
First in ClinVar: Feb 26, 2014 Last updated: Aug 13, 2015 |
Comment on evidence:
In 2 sibs of mixed European descent with JBTS21 (615636), Tuz et al. (2014) identified compound heterozygous mutations in the CSPP1 gene: a 2-bp deletion … (more)
In 2 sibs of mixed European descent with JBTS21 (615636), Tuz et al. (2014) identified compound heterozygous mutations in the CSPP1 gene: a 2-bp deletion (c.2244_2245delAA), resulting in a frameshift and premature termination (Glu750GlyfsTer30), and a 1-bp deletion (c.2280delA; 611654.0003), resulting in a frameshift and premature termination (Glu761LysfsTer35). The patients had a severe phenotype, with feeding abnormalities, nystagmus, short ribs, bell-shaped chest, and pulmonary hypoplasia. (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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Prospective Evaluation of Kidney Disease in Joubert Syndrome. | Fleming LR | Clinical journal of the American Society of Nephrology : CJASN | 2017 | PMID: 29146704 |
Characterizing the morbid genome of ciliopathies. | Shaheen R | Genome biology | 2016 | PMID: 27894351 |
Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity. | Bachmann-Gagescu R | Journal of medical genetics | 2015 | PMID: 26092869 |
Mutations in CSPP1 cause primary cilia abnormalities and Joubert syndrome with or without Jeune asphyxiating thoracic dystrophy. | Tuz K | American journal of human genetics | 2014 | PMID: 24360808 |
Mutations in CSPP1 lead to classical Joubert syndrome. | Akizu N | American journal of human genetics | 2014 | PMID: 24360807 |
Text-mined citations for rs587777139 ...
HelpRecord last updated Feb 20, 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.