ClinVar Genomic variation as it relates to human health
NM_001363711.2(DUOX2):c.1588A>T (p.Lys530Ter)
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_001363711.2(DUOX2):c.1588A>T (p.Lys530Ter)
Variation ID: 287079 Accession: VCV000287079.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 15q21.1 15: 45107450 (GRCh38) [ NCBI UCSC ] 15: 45399648 (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 Dec 6, 2016 Feb 20, 2024 Jan 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001363711.2:c.1588A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001350640.1:p.Lys530Ter nonsense NM_014080.5:c.1588A>T NP_054799.4:p.Lys530Ter nonsense NC_000015.10:g.45107450T>A NC_000015.9:g.45399648T>A NG_009447.1:g.11712A>T - Protein change
- K530*
- Other names
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- Canonical SPDI
- NC_000015.10:45107449:T: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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0.00060 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00017
1000 Genomes Project 0.00060
Trans-Omics for Precision Medicine (TOPMed) 0.00073
1000 Genomes Project 30x 0.00094
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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DUOX2 | - | - |
GRCh38 GRCh37 |
1890 | 1917 |
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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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jan 29, 2024 | RCV000329453.12 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Apr 7, 2022 | RCV000779165.11 |
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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Pathogenic
(Apr 15, 2016)
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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: SCV000340738.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Nov 21, 2018)
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criteria provided, single submitter
Method: clinical testing
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Thyroid dyshormonogenesis 6
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000915682.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The DUOX2 c.1588A>T (p.Lys530Ter) variant is a stop-gained variant that is predicted to result in premature truncation of the protein. Across a selection of available … (more)
The DUOX2 c.1588A>T (p.Lys530Ter) variant is a stop-gained variant that is predicted to result in premature truncation of the protein. Across a selection of available literature, the p.Lys530Ter variant has been found in at least 18 individuals with congenital hypothyroidism including one in a homozygous state, eight in a compound heterozygous state including a sibling pair and nine in a heterozygous state (Maruo et al. 2008; Fu et al. 2015; Fu et al. 2016; Chen et al. 2018). The sibling pair compound heterozygous for the variant inherited the p.Lys530Ter variant from their unaffected mother (Maruo et al. 2008). The p.Lys530Ter variant was absent from 200 control individuals and is reported at a frequency of 0.009274 in the East Asian population of the Genome Aggregation Database, which includes two homozygotes. Based on the collective evidence and the potential impact of stop-gained variants, the p.Lys530Ter variant is classified as pathogenic for congenital hypothyroidism. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Pathogenic
(Sep 19, 2019)
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criteria provided, single submitter
Method: clinical testing
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Thyroid dyshormonogenesis 6
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001519890.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
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Pathogenic
(Jun 07, 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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GeneDx
Accession: SCV002762468.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 27557340, 29650690, 25525159, 27498126, 29092890, 28222800, 30022773, 31980526, 33628596, 34276565, 32319661, 27108200, 26349762, 18765513, 30154845) (less)
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Pathogenic
(Apr 07, 2022)
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criteria provided, single submitter
Method: clinical testing
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Thyroid dyshormonogenesis 6
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002811545.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Jul 28, 2021)
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criteria provided, single submitter
Method: clinical testing
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Thyroid dyshormonogenesis 6
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002021808.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 29, 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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Invitae
Accession: SCV001205928.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Lys530*) in the DUOX2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Lys530*) in the DUOX2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DUOX2 are known to be pathogenic (PMID: 12110737, 18765513, 21565790, 24423310, 24735383). This variant is present in population databases (rs180671269, gnomAD 0.9%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with congenital hypothyroidism (PMID: 18765513, 26349762, 27108200). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 287079). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 06, 2020)
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no assertion criteria provided
Method: curation
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Thyroid dyshormonogenesis 6
Affected status: unknown
Allele origin:
germline
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Reproductive Health Research and Development, BGI Genomics
Accession: SCV001142448.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
Comment:
NM_014080.4:c.1588A>T in the DUOX2 gene has an allele frequency of 0.009 in East Asian subpopulation in the gnomAD database. This variant is located in the … (more)
NM_014080.4:c.1588A>T in the DUOX2 gene has an allele frequency of 0.009 in East Asian subpopulation in the gnomAD database. This variant is located in the 14th exon (34 exons in the NM_014080.4 transcript), therefore, it predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1588A>T variant has been reported multiple times in patients either in homozygosity or compound heterozygosity, for example, c.[1588A>T];[2635G>A] (PMID: 18765513), c.[1588A>T];[1588A>T] (PMID: 27108200), c.[1588A>T];[3340delC] (PMID: 26349762). Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP criteria applied: PVS1; PS4. (less)
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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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Mutational Spectrum Analysis of Seven Genes Associated with Thyroid Dyshormonogenesis. | Chen X | International journal of endocrinology | 2018 | PMID: 30154845 |
Next-generation sequencing analysis of DUOX2 in 192 Chinese subclinical congenital hypothyroidism (SCH) and CH patients. | Fu C | Clinica chimica acta; international journal of clinical chemistry | 2016 | PMID: 27108200 |
Genotypes and phenotypes of congenital goitre and hypothyroidism caused by mutations in dual oxidase 2 genes. | Wang F | Clinical endocrinology | 2014 | PMID: 24735383 |
The clinical and molecular characterization of patients with dyshormonogenic congenital hypothyroidism reveals specific diagnostic clues for DUOX2 defects. | Muzza M | The Journal of clinical endocrinology and metabolism | 2014 | PMID: 24423310 |
Identification and functional analysis of novel dual oxidase 2 (DUOX2) mutations in children with congenital or subclinical hypothyroidism. | De Marco G | The Journal of clinical endocrinology and metabolism | 2011 | PMID: 21565790 |
Transient congenital hypothyroidism caused by biallelic mutations of the dual oxidase 2 gene in Japanese patients detected by a neonatal screening program. | Maruo Y | The Journal of clinical endocrinology and metabolism | 2008 | PMID: 18765513 |
Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism. | Moreno JC | The New England journal of medicine | 2002 | PMID: 12110737 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DUOX2 | - | - | - | - |
Text-mined citations for rs180671269 ...
HelpRecord last updated Mar 17, 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.