ClinVar Genomic variation as it relates to human health
NM_000396.4(CTSK):c.263A>C (p.Gln88Pro)
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_000396.4(CTSK):c.263A>C (p.Gln88Pro)
Variation ID: 553629 Accession: VCV000553629.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q21.3 1: 150805997 (GRCh38) [ NCBI UCSC ] 1: 150778473 (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 5, 2018 Dec 30, 2023 Dec 28, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000396.4:c.263A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000387.1:p.Gln88Pro missense NC_000001.11:g.150805997T>G NC_000001.10:g.150778473T>G NG_011848.1:g.7340A>C - Protein change
- Q88P
- Other names
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- Canonical SPDI
- NC_000001.11:150805996:T: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.
The Genome Aggregation Database (gnomAD) 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Exome Aggregation Consortium (ExAC) 0.00017
- 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
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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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CTSK | - | - |
GRCh38 GRCh37 |
374 | 386 |
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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Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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Dec 28, 2023 | RCV000669116.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jul 26, 2021 | RCV001553728.1 |
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
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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Uncertain significance
(Nov 14, 2017)
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criteria provided, single submitter
Method: clinical testing
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Pyknodysostosis
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000793829.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Uncertain significance
(Jul 26, 2021)
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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: SCV001774710.1
First in ClinVar: Aug 07, 2021 Last updated: Aug 07, 2021 |
Comment:
Variant summary: CTSK c.263A>C (p.Gln88Pro) results in a non-conservative amino acid change located in the CTSK proregion (Pangrazio_2014) of the encoded protein sequence. Three of … (more)
Variant summary: CTSK c.263A>C (p.Gln88Pro) results in a non-conservative amino acid change located in the CTSK proregion (Pangrazio_2014) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 251436 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CTSK causing Pyknodysostosis (0.00012 vs 0.0011), allowing no conclusion about variant significance. c.263A>C has been reported in the literature in at-least one comprehensively genotyped (WES) homozygous individual affected with mild Osteoporosis (example, Pangrazio_2014) and subsequently cited by others. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. (less)
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Uncertain significance
(Apr 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Pyknodysostosis
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV004049731.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
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Uncertain significance
(Dec 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Pyknodysostosis
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
maternal
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Human Genetics Unit, University Of Colombo
Accession: SCV004218418.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
Comment:
This variant was observed in compound heterozygosity with variant (NM_000396.3:c.568C>T)
Number of individuals with the variant: 2
Clinical Features:
Failure to thrive (present) , Short stature (present) , Craniosynostosis syndrome (present) , Dolichocephaly (present) , Genu varum (present) , Proptosis (present) , Elevated circulating … (more)
Failure to thrive (present) , Short stature (present) , Craniosynostosis syndrome (present) , Dolichocephaly (present) , Genu varum (present) , Proptosis (present) , Elevated circulating alkaline phosphatase concentration (present) , Low levels of vitamin D (present) , Hyperphosphatemia (present) , Hypocalcemia (present) , Increased bone mineral density (present) , Increased intracranial pressure (present) , Encephalocele (present) , Elevated circulating parathyroid hormone level (present) (less)
Family history: no
Ethnicity/Population group: Sinhalese
Geographic origin: Sri Lanka;South Asia
Secondary finding: no
Testing laboratory: Centogene AG - the Rare Disease Company
Date variant was reported to submitter: 2022-07-29
Testing laboratory interpretation: Uncertain significance
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Uncertain significance
(Feb 20, 2020)
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no assertion criteria provided
Method: clinical testing
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Pyknodysostosis
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002085808.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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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The genotypic and phenotypic spectrum of pycnodysostosis in Saudi Arabia: Novel variants and clinical findings. | Mushiba AM | American journal of medical genetics. Part A | 2021 | PMID: 33963797 |
Pycnodysostosis: Natural history and management guidelines from 27 French cases and a literature review. | Bizaoui V | Clinical genetics | 2019 | PMID: 31237352 |
Pycnodysostosis: Novel Variants in CTSK and Occurrence of Giant Cell Tumor. | Shambhavi A | Journal of pediatric genetics | 2018 | PMID: 29441215 |
Molecular analysis of the CTSK gene in a cohort of 33 Brazilian families with pycnodysostosis from a cluster in a Brazilian Northeast region. | Araujo TF | European journal of medical research | 2016 | PMID: 27558267 |
Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis. | Pangrazio A | Bone | 2014 | PMID: 24269275 |
Text-mined citations for rs762212949 ...
HelpRecord last updated Jan 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.