Frameshift variant predicted to result in protein truncation, as the last 99 amino acids are replaced with 20 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34853893, 34645488, 19853239, 31585110, 28229453, 20425819, 31130284, 32860008, 29620724, 34406647, 36331722)
ClinVar Genomic variation as it relates to human health
NM_001159773.2(CANT1):c.902_906dup (p.Ser303fs)
Germline
Classification
Help
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.
(10)
Help
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/Likely pathogenic
10
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001159773.2(CANT1):c.902_906dup (p.Ser303fs)
Variation ID: 31013 Accession: VCV000031013.41
- Type and length
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Microsatellite, 5 bp
- Location
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Cytogenetic: 17q25.3 17: 78993849-78993850 (GRCh38) [ NCBI UCSC ] 17: 76989931-76989932 (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 11, 2015 Oct 8, 2024 Mar 25, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001159773.2:c.902_906dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001153245.1:p.Ser303fs frameshift NM_001159773.2:c.906_907insGCGCC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001159772.1:c.902_906dup NM_001159772.2:c.902_906dup NP_001153244.1:p.Ser303fs frameshift NM_138793.3:c.902_906dupGCGCC NM_138793.4:c.902_906dup NP_620148.1:p.Ser303fs frameshift NC_000017.11:g.78993853GCGGC[3] NC_000017.10:g.76989935GCGGC[3] NG_016645.1:g.20959GCGCC[3] - Protein change
- S303fs
- Other names
- -
- Canonical SPDI
- NC_000017.11:78993849:GGCGCGGCGCGGC:GGCGCGGCGCGGCGCGGC
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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.
- -
- Links
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. |
|||
| CANT1 | - | - |
GRCh38 GRCh37 |
403 | 438 | |
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/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Mar 25, 2024 | RCV000024005.16 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Dec 26, 2023 | RCV000726652.11 | |
|
CANT1-related disorder
|
Pathogenic (1) |
no assertion criteria provided
|
Nov 6, 2023 | RCV003904861.2 |
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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|---|---|---|---|---|---|
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Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Desbuquois dysplasia 1
Affected status: yes
Allele origin:
germline
|
Centogene AG - the Rare Disease Company
Accession: SCV001426589.1
First in ClinVar: Aug 09, 2020 Last updated: Aug 09, 2020 |
|
|
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Likely pathogenic
(Mar 25, 2024)
|
criteria provided, single submitter
Method: research
|
Desbuquois dysplasia 1
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004805417.2
First in ClinVar: Mar 30, 2024 Last updated: Apr 06, 2024 |
|
|
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Pathogenic
(May 21, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000701968.2
First in ClinVar: Apr 02, 2018 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 8
Sex: mixed
|
|
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Pathogenic
(Nov 30, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: yes
Allele origin:
germline
|
Blueprint Genetics
Accession: SCV001832321.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021
Comment:
Patient analyzed with Comprehensive Skeletal Dysplasias and Disorders Panel
|
|
|
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Pathogenic
(Jun 13, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001790795.2
First in ClinVar: Aug 21, 2021 Last updated: Jun 24, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation, as the last 99 amino acids are replaced with 20 different amino acids, and other loss-of-function variants … (more)
Frameshift variant predicted to result in protein truncation, as the last 99 amino acids are replaced with 20 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34853893, 34645488, 19853239, 31585110, 28229453, 20425819, 31130284, 32860008, 29620724, 34406647, 36331722) (less)
|
|
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Pathogenic
(Dec 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004297572.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ser303Alafs*21) in the CANT1 gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Ser303Alafs*21) in the CANT1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 99 amino acid(s) of the CANT1 protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with Desbuquois dysplasia (PMID: 19853239, 28229453, 29620724). ClinVar contains an entry for this variant (Variation ID: 31013). For these reasons, this variant has been classified as Pathogenic. (less)
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|
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Pathogenic
(May 01, 2010)
|
no assertion criteria provided
Method: literature only
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DESBUQUOIS DYSPLASIA 1
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000045296.4
First in ClinVar: Apr 04, 2013 Last updated: Oct 11, 2015 |
Comment on evidence:
In a male infant, born of consanguineous Saudi Arabian parents, with Desbuquois dysplasia-1 (DBQD1; 251450), Faden et al. (2010) identified a homozygous 5-bp duplication (893_894insGCCGC) … (more)
In a male infant, born of consanguineous Saudi Arabian parents, with Desbuquois dysplasia-1 (DBQD1; 251450), Faden et al. (2010) identified a homozygous 5-bp duplication (893_894insGCCGC) in exon 4 of the CANT1 gene, resulting in a frameshift and premature termination of the protein at codon 325. The patient had micromelia, severe growth retardation, clubfeet, dysmorphic facial features, hypotonia, short neck, widely spaced nipples, and protuberant abdomen. Radiographs showed typical hand findings with 2 supernumerary ossification centers and phalangeal dislocations, vertebral bodies with coronal clefting, and spur-like projections in the lesser trochanters. He also had bilateral congenital glaucoma. Three older sibs had died in the neonatal period of a similar disorder. (less)
|
|
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Pathogenic
(Apr 29, 2021)
|
no assertion criteria provided
Method: research
|
Desbuquois dysplasia 1
Affected status: yes
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV001870447.1
First in ClinVar: Mar 12, 2022 Last updated: Mar 12, 2022 |
|
|
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Pathogenic
(Jan 30, 2022)
|
no assertion criteria provided
Method: clinical testing
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Desbuquois dysplasia 1
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital
Accession: SCV002072475.1
First in ClinVar: Feb 05, 2022 Last updated: Feb 05, 2022 |
Comment:
The homozygous frameshift insertion variant c.906_907insGCGCC (p.S303Afs*20) has been previously reported by Huber C et al in 2009 in a Moroccan patient. The allele frequency … (more)
The homozygous frameshift insertion variant c.906_907insGCGCC (p.S303Afs*20) has been previously reported by Huber C et al in 2009 in a Moroccan patient. The allele frequency is 0.0008% in gnomAD (aggregated) database. In-silico bioinformatic software predict this variant by mutation taster as Disease causing. The phenotype observed was micromelia, monkey wrench feature. Desbuquois Dysplasia 1 is an autosomal recessive disorder. Based on the phenotypic observation, we classify this variant as pathogenic. (less)
Ethnicity/Population group: South East Asian
Geographic origin: India
|
|
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Pathogenic
(Nov 06, 2023)
|
no assertion criteria provided
Method: clinical testing
|
CANT1-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004728274.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
The CANT1 c.902_906dup5 variant is predicted to result in a frameshift and premature protein termination (p.Ser303Alafs*21). This variant was reported in multiple individuals with autosomal … (more)
The CANT1 c.902_906dup5 variant is predicted to result in a frameshift and premature protein termination (p.Ser303Alafs*21). This variant was reported in multiple individuals with autosomal recessive Desbuquois dysplasia (Huber. 2009. PubMed ID: 19853239; Al-Hamed. 2021. PubMed ID: 34853893; Table S6, Maddirevula. 2018. PubMed ID: 29620724; Ranza. 2017. PubMed ID: 28229453). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-76989931-T-TGGCGC). Frameshift variants in CANT1 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
|
Comment:
Comment:
This sequence change creates a premature translational stop signal (p.Ser303Alafs*21) in the CANT1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 99 amino acid(s) of the CANT1 protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with Desbuquois dysplasia (PMID: 19853239, 28229453, 29620724). ClinVar contains an entry for this variant (Variation ID: 31013). For these reasons, this variant has been classified as Pathogenic.
Comment:
The homozygous frameshift insertion variant c.906_907insGCGCC (p.S303Afs*20) has been previously reported by Huber C et al in 2009 in a Moroccan patient. The allele frequency is 0.0008% in gnomAD (aggregated) database. In-silico bioinformatic software predict this variant by mutation taster as Disease causing. The phenotype observed was micromelia, monkey wrench feature. Desbuquois Dysplasia 1 is an autosomal recessive disorder. Based on the phenotypic observation, we classify this variant as pathogenic.
Comment:
The CANT1 c.902_906dup5 variant is predicted to result in a frameshift and premature protein termination (p.Ser303Alafs*21). This variant was reported in multiple individuals with autosomal recessive Desbuquois dysplasia (Huber. 2009. PubMed ID: 19853239; Al-Hamed. 2021. PubMed ID: 34853893; Table S6, Maddirevula. 2018. PubMed ID: 29620724; Ranza. 2017. PubMed ID: 28229453). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-76989931-T-TGGCGC). Frameshift variants in CANT1 are expected to be pathogenic. This variant is interpreted as pathogenic.
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. |
Comment:
Frameshift variant predicted to result in protein truncation, as the last 99 amino acids are replaced with 20 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34853893, 34645488, 19853239, 31585110, 28229453, 20425819, 31130284, 32860008, 29620724, 34406647, 36331722)
Comment:
This sequence change creates a premature translational stop signal (p.Ser303Alafs*21) in the CANT1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 99 amino acid(s) of the CANT1 protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with Desbuquois dysplasia (PMID: 19853239, 28229453, 29620724). ClinVar contains an entry for this variant (Variation ID: 31013). For these reasons, this variant has been classified as Pathogenic.
Comment:
The homozygous frameshift insertion variant c.906_907insGCGCC (p.S303Afs*20) has been previously reported by Huber C et al in 2009 in a Moroccan patient. The allele frequency is 0.0008% in gnomAD (aggregated) database. In-silico bioinformatic software predict this variant by mutation taster as Disease causing. The phenotype observed was micromelia, monkey wrench feature. Desbuquois Dysplasia 1 is an autosomal recessive disorder. Based on the phenotypic observation, we classify this variant as pathogenic.
Comment:
The CANT1 c.902_906dup5 variant is predicted to result in a frameshift and premature protein termination (p.Ser303Alafs*21). This variant was reported in multiple individuals with autosomal recessive Desbuquois dysplasia (Huber. 2009. PubMed ID: 19853239; Al-Hamed. 2021. PubMed ID: 34853893; Table S6, Maddirevula. 2018. PubMed ID: 29620724; Ranza. 2017. PubMed ID: 28229453). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-76989931-T-TGGCGC). Frameshift variants in CANT1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Successful application of genome sequencing in a diagnostic setting: 1007 index cases from a clinically heterogeneous cohort. | Bertoli-Avella AM | European journal of human genetics : EJHG | 2021 | PMID: 32860008 |
| Expanding the phenome and variome of skeletal dysplasia. | Maddirevula S | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29620724 |
| Chondrodysplasia with multiple dislocations: comprehensive study of a series of 30 cases. | Ranza E | Clinical genetics | 2017 | PMID: 28229453 |
| Mutation of CANT1 causes Desbuquois dysplasia. | Faden M | American journal of medical genetics. Part A | 2010 | PMID: 20425819 |
| Identification of CANT1 mutations in Desbuquois dysplasia. | Huber C | American journal of human genetics | 2009 | PMID: 19853239 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CANT1 | - | - | - | - |
Text-mined citations for rs587776895 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 27, 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.