ClinVar Genomic variation as it relates to human health
NM_001347721.2(DYRK1A):c.924+4_924+7del
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_001347721.2(DYRK1A):c.924+4_924+7del
Variation ID: 435011 Accession: VCV000435011.34
- Type and length
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Deletion, 4 bp
- Location
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Cytogenetic: 21q22.13 21: 37490462-37490465 (GRCh38) [ NCBI UCSC ] 21: 38862764-38862767 (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 28, 2017 Apr 15, 2024 Feb 23, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001347721.2:c.924+4_924+7del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001347722.2:c.924+4_924+7del splice donor NM_001347723.2:c.837+4_837+7del splice donor NM_001396.3:c.951+1_951+4delGTAA NM_001396.3:c.951+4_951+7del NM_001396.3:c.951+4_951+7delAGTA NM_001396.5:c.951+4_951+7del splice donor NM_101395.2:c.951+4_951+7del splice donor NM_130436.2:c.924+4_924+7del splice donor NM_130438.2:c.951+4_951+7del splice donor NC_000021.9:g.37490465_37490468del NC_000021.8:g.38862767_38862770del NG_009366.1:g.127909_127912del - Protein change
- Other names
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- Canonical SPDI
- NC_000021.9:37490461:GTAAGTA:GTA
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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
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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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DYRK1A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
958 | 1032 |
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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Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Feb 23, 2023 | RCV000501673.18 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 5, 2023 | RCV000599528.18 | |
Likely pathogenic (1) |
no assertion criteria provided
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Dec 4, 2018 | RCV001265140.3 |
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
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
(Feb 16, 2017)
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criteria provided, single submitter
Method: clinical testing
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Mental retardation, autosomal dominant 7
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000594475.1
First in ClinVar: Aug 28, 2017 Last updated: Aug 28, 2017 |
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Likely pathogenic
(Jan 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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DYRK1A-related intellectual disability syndrome
Affected status: yes
Allele origin:
de novo
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Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV000965731.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
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Likely pathogenic
(Jan 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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DYRK1A-related intellectual disability syndrome
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001370159.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2.
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Pathogenic
(Jan 05, 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: SCV000709803.4
First in ClinVar: Apr 02, 2018 Last updated: Jan 15, 2023 |
Comment:
Functional studies demonstrate abnormal gene splicing with skipping of exon 6 (Luco et al., 2016); In silico analysis supports a deleterious effect on splicing; Not … (more)
Functional studies demonstrate abnormal gene splicing with skipping of exon 6 (Luco et al., 2016); In silico analysis supports a deleterious effect on splicing; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26922654, 27241786, 34345024, 33562844, 33004838, 35709690) (less)
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Pathogenic
(Feb 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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DYRK1A-related intellectual disability syndrome
Affected status: yes
Allele origin:
unknown
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3billion
Accession: SCV003842142.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to alter splicing and result in a loss or disruption of … (more)
The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been previously reported as de novo in a similarly affected individual (PMID: 26922654). The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000435011 / PMID: 26922654 / 3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Macrotia (present) , Slender finger (present) , Severe global developmental delay (present) , Decreased body weight (present) , Autistic behavior (present)
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Pathogenic
(Jan 24, 2020)
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criteria provided, single submitter
Method: clinical testing
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DYRK1A-related intellectual disability syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000660433.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: … (more)
For these reasons, this variant has been classified as Pathogenic. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). RT-PCR and sequencing of the mRNA derived from the individual with this variant showed exon 7 skipping (PMID: 26922654). Exon 7 is referred to as exon 6 in the literature. This variant has been shown to arise de novo in an individual affected with syndromic intellectual disability, with features consistent with a DYRK1A-related disorder (PMID: 26922654, 27241786, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 6 of the DYRK1A gene. It does not directly change the encoded amino acid sequence of the DYRK1A protein, but it affects a nucleotide within the consensus splice site of the intron. (less)
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Pathogenic
(Aug 01, 2021)
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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: SCV001962416.14
First in ClinVar: Oct 08, 2021 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Likely pathogenic
(Dec 04, 2018)
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no assertion criteria provided
Method: provider interpretation
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Complex neurodevelopmental disorder
Affected status: yes
Allele origin:
de novo,
unknown
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GenomeConnect - Simons Searchlight
Accession: SCV001443175.1
First in ClinVar: Nov 19, 2020 Last updated: Nov 19, 2020 |
Comment:
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-12-04 and interpreted as Likely Pathogenic. The reporting … (more)
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-12-04 and interpreted as Likely Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight. (less)
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Autistic behavior (present) , Induced vaginal delivery (present) , Hypertonia (present) , Microcephaly (present) , Seizure precipitated by febrile infection (present) , Seizures (present) , … (more)
Autistic behavior (present) , Induced vaginal delivery (present) , Hypertonia (present) , Microcephaly (present) , Seizure precipitated by febrile infection (present) , Seizures (present) , Generalized tonic-clonic seizures (present) , Absence seizures (present) , Gastroesophageal reflux (present) , Constipation (present) , Otitis media (present) , Failure to thrive (present) , Abnormality of the skin (present) , Eczema (present) , Allergy (present) , Drug allergy (present) , Allergic rhinitis (present) (less)
Age: 10-19 years
Sex: male
Testing laboratory: GeneDx
Testing laboratory interpretation: Pathogenic
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Decreased fetal movement (present) , Caesarian section (present) , Placental abruption (present) , Neonatal respiratory distress (present) , Neonatal seizure (present) , Hypertonia (present) , … (more)
Decreased fetal movement (present) , Caesarian section (present) , Placental abruption (present) , Neonatal respiratory distress (present) , Neonatal seizure (present) , Hypertonia (present) , Microcephaly (present) , Cerebral palsy (present) , Seizures (present) , Generalized tonic-clonic seizures (present) , Absence seizures (present) , Focal seizures with impairment of consciousness or awareness (present) , Gastroesophageal reflux (present) , Diarrhea (present) , Constipation (present) , Otitis media (present) , Pneumonia (present) , Abnormality of the respiratory system (present) , Asthma (present) , Chronic lung disease (present) , Abnormal heart morphology (present) , Atrial septal defect (present) , Failure to thrive (present) , Short stature (present) , Abnormality of the skin (present) , Eczema (present) , Allergy (present) , Drug allergy (present) , Food allergy (present) , Abnormality of the cardiovascular system (present) , Tonic seizure (present) , Abnormality of the vasculature (present) , Abnormality of temperature regulation (present) , Abnormality of the dentition (present) , Sleep disturbance (present) (less)
Age: 0-9 years
Sex: female
Testing laboratory: Genetic Services Laboratory,University of Chicago
Testing laboratory interpretation: Likely pathogenic
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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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Next-generation sequencing for diagnosis of rare diseases in the neonatal intensive care unit. | Daoud H | CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne | 2016 | PMID: 27241786 |
Case report of novel DYRK1A mutations in 2 individuals with syndromic intellectual disability and a review of the literature. | Luco SM | BMC medical genetics | 2016 | PMID: 26922654 |
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
Text-mined citations for rs1555984461 ...
HelpRecord last updated Apr 15, 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.