ClinVar Genomic variation as it relates to human health
NM_001363.5(DKC1):c.838A>C (p.Ser280Arg)
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_001363.5(DKC1):c.838A>C (p.Ser280Arg)
Variation ID: 38952 Accession: VCV000038952.25
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 154769233 (GRCh38) [ NCBI UCSC ] X: 153997508 (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 Apr 4, 2013 May 1, 2024 Jan 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001363.5:c.838A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001354.1:p.Ser280Arg missense NM_001142463.3:c.838A>C NP_001135935.1:p.Ser280Arg missense NM_001288747.2:c.838A>C NP_001275676.1:p.Ser280Arg missense NR_110021.2:n.1417A>C non-coding transcript variant NR_110022.2:n.1536A>C non-coding transcript variant NR_110023.2:n.1310A>C non-coding transcript variant NC_000023.11:g.154769233A>C NC_000023.10:g.153997508A>C NG_009780.1:g.11478A>C LRG_55:g.11478A>C LRG_55t1:c.838A>C - Protein change
- S280R
- Other names
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- Canonical SPDI
- NC_000023.11:154769232:A:C
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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.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00019
Trans-Omics for Precision Medicine (TOPMed) 0.00020
The Genome Aggregation Database (gnomAD), exomes 0.00027
The Genome Aggregation Database (gnomAD) 0.00028
Exome Aggregation Consortium (ExAC) 0.00032
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
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. |
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DKC1 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
460 | 672 |
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. |
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Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Apr 7, 2022 | RCV000032203.5 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Jan 29, 2024 | RCV000634503.11 | |
Likely benign (1) |
criteria provided, single submitter
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May 21, 2021 | RCV004018698.1 | |
Likely benign (4) |
criteria provided, single submitter
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Dec 1, 2022 | RCV001573922.8 |
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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Likely benign
(Nov 15, 2021)
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criteria provided, single submitter
Method: curation
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Dyskeratosis congenita
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002535834.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Benign
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Dyskeratosis congenita
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000755819.7
First in ClinVar: May 28, 2018 Last updated: Feb 20, 2024 |
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Likely benign
(May 21, 2021)
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criteria provided, single submitter
Method: clinical testing
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DKC1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004750499.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Likely benign
(Dec 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: SCV004165999.4
First in ClinVar: Nov 20, 2023 Last updated: Apr 15, 2024 |
Comment:
DKC1: PP2, BS2
Number of individuals with the variant: 1
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Likely benign
(Feb 02, 2022)
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criteria provided, single submitter
Method: clinical testing
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Dyskeratosis congenita, X-linked
Affected status: unknown
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002767331.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as likely benign. Following criteria are met: 0308 - Population frequency for this variant is … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as likely benign. Following criteria are met: 0308 - Population frequency for this variant is out of keeping with known incidence of X-linked recessive dyskeratosis congenita (MIM#305000). (SB) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Benign
(Apr 07, 2022)
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criteria provided, single submitter
Method: clinical testing
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Dyskeratosis congenita, X-linked
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002809283.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Benign
(Aug 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Dyskeratosis congenita
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002678754.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001800481.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001969976.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001958751.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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not provided
(-)
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no classification provided
Method: literature only
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Dyskeratosis congenita, X-linked
Affected status: not provided
Allele origin:
unknown
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GeneReviews
Accession: SCV000055795.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 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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Dyskeratosis Congenita and Related Telomere Biology Disorders. | Adam MP | - | 2023 | PMID: 20301779 |
Gene Panel Testing in Hereditary Breast Cancer. | Rostami P | Archives of Iranian medicine | 2020 | PMID: 32126783 |
Rare Protein-Altering Telomere-related Gene Variants in Patients with Chronic Hypersensitivity Pneumonitis. | Ley B | American journal of respiratory and critical care medicine | 2019 | PMID: 31268371 |
Clinical implications of systematic phenotyping and exome sequencing in patients with primary antibody deficiency. | Abolhassani H | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 29921932 |
Pathogenic Germline Variants in 10,389 Adult Cancers. | Huang KL | Cell | 2018 | PMID: 29625052 |
Clonal hematopoiesis in patients with dyskeratosis congenita. | Perdigones N | American journal of hematology | 2016 | PMID: 27622320 |
Effects of dyskeratosis congenita mutations in dyskerin, NHP2 and NOP10 on assembly of H/ACA pre-RNPs. | Trahan C | Human molecular genetics | 2010 | PMID: 20008900 |
Identification of novel DKC1 mutations in patients with dyskeratosis congenita: implications for pathophysiology and diagnosis. | Knight SW | Human genetics | 2001 | PMID: 11379875 |
Text-mined citations for rs146700772 ...
HelpRecord last updated May 01, 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.