ClinVar Genomic variation as it relates to human health
NM_000782.5(CYP24A1):c.62del (p.Pro21fs)
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_000782.5(CYP24A1):c.62del (p.Pro21fs)
Variation ID: 632376 Accession: VCV000632376.16
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 20q13.2 20: 54173518 (GRCh38) [ NCBI UCSC ] 20: 52790057 (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 May 27, 2019 Feb 28, 2024 Apr 20, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000782.5:c.62del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000773.2:p.Pro21fs frameshift NM_000782.5:c.62delC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000782.4:c.62del NM_001128915.2:c.62del NP_001122387.1:p.Pro21fs frameshift NC_000020.11:g.54173519del NC_000020.10:g.52790058del NG_008334.1:g.5460del - Protein change
- P21fs
- Other names
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- Canonical SPDI
- NC_000020.11:54173517:GG: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
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The frequency of the allele represented by this VCV record.
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- Links
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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CYP24A1 | - | - |
GRCh38 GRCh37 |
304 | 315 |
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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Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Apr 20, 2023 | RCV000779350.10 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 24, 2023 | RCV001856172.7 |
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
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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
(Jan 08, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hypercalcemia, infantile, 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000915945.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The CYP24A1 c.62delC (p.Pro21ArgfsTer8) variant results in a frameshift, and is predicted to result in premature termination of the protein. This variant has been reported … (more)
The CYP24A1 c.62delC (p.Pro21ArgfsTer8) variant results in a frameshift, and is predicted to result in premature termination of the protein. This variant has been reported in two studies and is found in two adults approximately 50 years of age with hypercalcuria, hypercalcemia, or calcium pyrophosphate deposition disease in a compound heterozygous state (Molin et al. 2015; Baudart et al. 2017). Control data are not available for this variant, but it is reported at a frequency of 0.00007172 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the evidence, the p.Pro21ArgfsTer8 variant is classified as likely pathogenic for hypercalcemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Pathogenic
(Dec 22, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hypercalcemia, infantile, 1
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV001752552.2
First in ClinVar: Jul 18, 2021 Last updated: Dec 31, 2022 |
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Pathogenic
(Apr 20, 2023)
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criteria provided, single submitter
Method: research
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Hypercalcemia, infantile, 1
Affected status: yes
Allele origin:
paternal
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Duke University Health System Sequencing Clinic, Duke University Health System
Accession: SCV003919043.1
First in ClinVar: Apr 30, 2023 Last updated: Apr 30, 2023 |
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Likely pathogenic
(Jan 24, 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: SCV003936221.1
First in ClinVar: Jul 08, 2023 Last updated: Jul 08, 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 … (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: 34721296, 26214117, 25446019, 33288743, 34307984, 28109821, 31188746) (less)
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Pathogenic
(Jun 08, 2022)
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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: SCV002232905.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 632376). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 632376). This premature translational stop signal has been observed in individual(s) with infantile hypercalcemia (PMID: 25446019). This variant is present in population databases (rs774432244, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Pro21Argfs*8) in the CYP24A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYP24A1 are known to be pathogenic (PMID: 21675912). (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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Calcium pyrophosphate deposition disease revealing a hypersensitivity to vitamin D. | Baudart P | Joint bone spine | 2017 | PMID: 28109821 |
CYP24A1 Mutations in a Cohort of Hypercalcemic Patients: Evidence for a Recessive Trait. | Molin A | The Journal of clinical endocrinology and metabolism | 2015 | PMID: 26214117 |
Kidney function and influence of sunlight exposure in patients with impaired 24-hydroxylation of vitamin D due to CYP24A1 mutations. | Figueres ML | American journal of kidney diseases : the official journal of the National Kidney Foundation | 2015 | PMID: 25446019 |
Mutations in CYP24A1 and idiopathic infantile hypercalcemia. | Schlingmann KP | The New England journal of medicine | 2011 | PMID: 21675912 |
Text-mined citations for rs774432244 ...
HelpRecord last updated Feb 28, 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.