ClinVar Genomic variation as it relates to human health
NM_001195553.2(DCX):c.814C>T (p.Arg272Ter)
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_001195553.2(DCX):c.814C>T (p.Arg272Ter)
Variation ID: 158509 Accession: VCV000158509.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq23 X: 111331036 (GRCh38) [ NCBI UCSC ] X: 110574264 (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 Nov 23, 2014 Feb 14, 2024 Sep 16, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001195553.2:c.814C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001182482.1:p.Arg272Ter nonsense NM_000555.3:c.1057C>T NP_000546.2:p.Arg353Ter nonsense NM_001369370.1:c.814C>T NP_001356299.1:p.Arg272Ter nonsense NM_001369371.1:c.814C>T NP_001356300.1:p.Arg272Ter nonsense NM_001369372.1:c.814C>T NP_001356301.1:p.Arg272Ter nonsense NM_001369373.1:c.814C>T NP_001356302.1:p.Arg272Ter nonsense NM_001369374.1:c.814C>T NP_001356303.1:p.Arg272Ter nonsense NM_178151.3:c.814C>T NP_835364.1:p.Arg272Ter nonsense NM_178152.3:c.814C>T NP_835365.1:p.Arg272Ter nonsense NM_178153.2:c.814C>T NM_178153.3:c.814C>T NP_835366.1:p.Arg272Ter nonsense NC_000023.11:g.111331036G>A NC_000023.10:g.110574264G>A NG_011750.1:g.86143C>T - Protein change
- R272*, R353*
- Other names
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- Canonical SPDI
- NC_000023.11:111331035:G: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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DCX | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
273 | 438 |
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
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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 (1) |
criteria provided, single submitter
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May 21, 2014 | RCV000145893.6 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Sep 9, 2022 | RCV000255524.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 3, 2018 | RCV002415631.1 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Sep 16, 2022 | RCV002285145.1 |
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
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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
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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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Pathogenic
(May 21, 2014)
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criteria provided, single submitter
Method: clinical testing
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Abnormality of neuronal migration
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000193030.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
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Pathogenic
(Jan 09, 2019)
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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: SCV000321545.5
First in ClinVar: Oct 09, 2016 Last updated: Oct 09, 2016 |
Comment:
The R272X nonsense variant in the DCX gene has been reported previously in individuals with seizures and subcortical band heterotopia on MRI (Bahi-Buisson et al., … (more)
The R272X nonsense variant in the DCX gene has been reported previously in individuals with seizures and subcortical band heterotopia on MRI (Bahi-Buisson et al., 2012; Kato et al.,1999; Matsumoto et al., 2001). The clinical presentation associated with R272X is variable, as some individuals are noted to have severe intellectual disability and intractable epilepsy, while others are described with mild intellectual disability or normal intelligence and seizures that are well-controlled with anticonvulsants; this phenotypic range is attributed to skewed X-inactivation patterns in females (Bahi-Buisson et al., 2012; Kato et al., 1999; Matsumoto et al., 2001). The R272X variant is observed in 1/16444 (0.006%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. (less)
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Pathogenic
(Aug 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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Lissencephaly type 1 due to doublecortin gene mutation
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV002576414.1
First in ClinVar: Oct 01, 2022 Last updated: Oct 01, 2022 |
Comment:
This variant was identified as mosaic (app 30 %) Criteria applied: PVS1, PS4_MOD, PM2_SUP
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Pathogenic
(Dec 03, 2018)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002680336.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The p.R272* pathogenic mutation (also known as c.814C>T), located in coding exon 4 of the DCX gene, results from a C to T substitution at … (more)
The p.R272* pathogenic mutation (also known as c.814C>T), located in coding exon 4 of the DCX gene, results from a C to T substitution at nucleotide position 814. This changes the amino acid from an arginine to a stop codon within coding exon 4. This mutation has been detected in familial and sporadic cases of subcortical band heterotopia (SBH) and seizures (Kato M et al. Hum. Genet., 1999 Apr;104:341-4; Matsumoto N et al. Eur. J. Hum. Genet., 2001 Jan;9:5-12 Bahi-Buisson N et al. Brain, 2013 Jan;136:223-44). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(Sep 09, 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: SCV003445191.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 158509). 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: 158509). This premature translational stop signal has been observed in individual(s) with X-linked lissencephaly and subcortical band heterotopia (PMID: 10369164). This variant is present in population databases (rs587783590, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg272*) in the DCX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DCX are known to be pathogenic (PMID: 11175293, 23365099). (less)
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Pathogenic
(Sep 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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Lissencephaly type 1 due to doublecortin gene mutation
(X-linked inheritance)
Affected status: yes
Allele origin:
germline
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Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin
Additional submitter:
CUBI - Core Unit Bioinformatics, Berlin Institute of Health
Accession: SCV002574948.1
First in ClinVar: Oct 01, 2022 Last updated: Oct 01, 2022 |
Clinical Features:
Hypotonia (present) , Global developmental delay (present) , Gait disturbance (present) , Broad-based gait (present)
Sex: female
Tissue: Blood
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Pathogenic
(-)
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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: SCV001959860.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(-)
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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: SCV001968465.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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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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Novel DCX mutation-caused lissencephaly in a boy and very mild heterotopia in his mother. | Takeshita S | Pediatrics international : official journal of the Japan Pediatric Society | 2015 | PMID: 25868952 |
New insights into genotype-phenotype correlations for the doublecortin-related lissencephaly spectrum. | Bahi-Buisson N | Brain : a journal of neurology | 2013 | PMID: 23365099 |
Somatic mosaicism and variable penetrance in doublecortin-associated migration disorders. | Aigner L | Neurology | 2003 | PMID: 12552055 |
Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia. | Matsumoto N | European journal of human genetics : EJHG | 2001 | PMID: 11175293 |
Text-mined citations for rs587783590 ...
HelpRecord last updated Feb 14, 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.