ClinVar Genomic variation as it relates to human health
NM_080916.3(DGUOK):c.4G>T (p.Ala2Ser)
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.
Uncertain significance(3); Benign(2); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_080916.3(DGUOK):c.4G>T (p.Ala2Ser)
Variation ID: 193482 Accession: VCV000193482.54
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p13.1 2: 73926914 (GRCh38) [ NCBI UCSC ] 2: 74154041 (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 Jun 8, 2016 Oct 8, 2024 Mar 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_080916.3:c.4G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_550438.1:p.Ala2Ser missense NM_001318859.2:c.4G>T NP_001305788.1:p.Ala2Ser missense NM_001318860.2:c.-175G>T 5 prime UTR NM_001318861.2:c.-261G>T 5 prime UTR NM_001318862.2:c.-261G>T 5 prime UTR NM_001318863.2:c.-175G>T 5 prime UTR NM_080918.3:c.4G>T NP_550440.1:p.Ala2Ser missense NR_134893.2:n.35G>T non-coding transcript variant NR_134894.2:n.35G>T non-coding transcript variant NR_134895.2:n.35G>T non-coding transcript variant NR_134896.2:n.35G>T non-coding transcript variant NR_134897.2:n.35G>T non-coding transcript variant NR_134898.2:n.35G>T non-coding transcript variant NC_000002.12:g.73926914G>T NC_000002.11:g.74154041G>T NG_008044.1:g.5089G>T - Protein change
- A2S
- Other names
- p.A2S:GCC>TCC
- Canonical SPDI
- NC_000002.12:73926913:G:T
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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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0.00120 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00120
1000 Genomes Project 30x 0.00125
Exome Aggregation Consortium (ExAC) 0.00235
The Genome Aggregation Database (gnomAD), exomes 0.00255
The Genome Aggregation Database (gnomAD) 0.00280
Trans-Omics for Precision Medicine (TOPMed) 0.00325
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00338
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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DGUOK | - | - |
GRCh38 GRCh37 |
233 | 369 | |
LOC129934096 | - | - | - | GRCh38 | - | 74 |
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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Conflicting interpretations of pathogenicity (10) |
criteria provided, conflicting classifications
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Mar 1, 2024 | RCV000173554.55 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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May 28, 2019 | RCV000660620.19 | |
DGUOK-related disorder
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Likely benign (1) |
no assertion criteria provided
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Nov 12, 2021 | RCV003975258.2 |
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
(Mar 01, 2024)
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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: SCV000575220.31
First in ClinVar: Dec 06, 2016 Last updated: Oct 08, 2024 |
Comment:
DGUOK: BS2
Number of individuals with the variant: 11
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Uncertain significance
(Apr 03, 2018)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000224676.5
First in ClinVar: Jun 29, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 18
Sex: mixed
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001135900.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001297289.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Likely benign
(Nov 20, 2020)
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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: SCV000251319.11
First in ClinVar: Oct 11, 2015 Last updated: Dec 19, 2017 |
Comment:
This variant is associated with the following publications: (PMID: 19748572, 18828154, 22622127, 17073823)
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Uncertain Significance
(Jan 18, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000280759.1
First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016 |
Comment:
Converted during submission to Uncertain significance.
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Benign
(Jan 31, 2024)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001012539.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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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, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001923308.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 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: SCV001974064.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001553284.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The DGUOK p.Ala2Ser variant was identified as a compound heterozygous variant in two pediatric cases with mitochondrial DNA depletion syndrome (Mousson_de_Camaret_2007_PMID: 17073823; Buchaklian_2012_PMID: 22622127). The … (more)
The DGUOK p.Ala2Ser variant was identified as a compound heterozygous variant in two pediatric cases with mitochondrial DNA depletion syndrome (Mousson_de_Camaret_2007_PMID: 17073823; Buchaklian_2012_PMID: 22622127). The variant was identified in dbSNP (ID: rs147551003) and ClinVar (classified as uncertain significance by Children's Mercy Hospital, GeneDx, Mayo Clinic, EGL Genetic Diagnostics, CeGaT Praxis; and as benign by Invitae and Mendelics). The variant was identified in control databases in 727 of 281762 chromosomes (3 homozygous) at a frequency of 0.00258 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 570 of 128878 chromosomes (freq: 0.004423), Latino in 91 of 35430 chromosomes (freq: 0.002568), Other in 16 of 7212 chromosomes (freq: 0.002219), Ashkenazi Jewish in 11 of 10352 chromosomes (freq: 0.001063), African in 22 of 24908 chromosomes (freq: 0.000883), South Asian in 14 of 30616 chromosomes (freq: 0.000457) and European (Finnish) in 3 of 24434 chromosomes (freq: 0.000123), but was not observed in the East Asian population. The p.Ala2 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (less)
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Likely benign
(Nov 12, 2021)
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no assertion criteria provided
Method: clinical testing
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DGUOK-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004790999.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 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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Uncertain significance
(Mar 08, 2016)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000802859.2
First in ClinVar: Aug 04, 2018 Last updated: May 27, 2023 |
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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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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001742416.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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not provided
(-)
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no classification provided
Method: phenotyping only
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Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)
Affected status: unknown
Allele origin:
unknown
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GenomeConnect, ClinGen
Accession: SCV000986887.1
First in ClinVar: Aug 31, 2019 Last updated: Aug 31, 2019 |
Comment:
Variant interpretted as Uncertain significance and reported on 10/30/2014 by GTR ID 320384. GenomeConnect assertions are reported exactly as they appear on the patient-provided report … (more)
Variant interpretted as Uncertain significance and reported on 10/30/2014 by GTR ID 320384. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Abnormality of the chin (present) , Abnormality of eye movement (present) , Myopia (present) , Hypermetropia (present) , Cognitive impairment (present) , EEG abnormality (present) … (more)
Abnormality of the chin (present) , Abnormality of eye movement (present) , Myopia (present) , Hypermetropia (present) , Cognitive impairment (present) , EEG abnormality (present) , Generalized hypotonia (present) , Memory impairment (present) , Seizures (present) , Anxiety (present) , Depressivity (present) , Obsessive-compulsive behavior (present) , Abnormality of muscle physiology (present) , Misalignment of teeth (present) (less)
Age: 20-29 years
Sex: female
Testing laboratory: Courtagen
Date variant was reported to submitter: 2014-10-30
Testing laboratory interpretation: Uncertain significance
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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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Recessive deoxyguanosine kinase deficiency causes juvenile onset mitochondrial myopathy. | Buchaklian AH | Molecular genetics and metabolism | 2012 | PMID: 22622127 |
Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion. | Mousson de Camaret B | The Biochemical journal | 2007 | PMID: 17073823 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DGUOK | - | - | - | - |
Text-mined citations for rs147551003 ...
HelpRecord last updated Oct 08, 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.