ClinVar Genomic variation as it relates to human health
NM_001363711.2(DUOX2):c.3006-2A>G
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
-
NM_001363711.2(DUOX2):c.3006-2A>G
Variation ID: 1324302 Accession: VCV001324302.8
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 15q21.1 15: 45100230 (GRCh38) [ NCBI UCSC ] 15: 45392428 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 29, 2021 Oct 13, 2024 May 30, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001363711.2:c.3006-2A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_014080.5:c.3006-2A>G splice acceptor NC_000015.10:g.45100230T>C NC_000015.9:g.45392428T>C NG_009447.1:g.18932A>G - Protein change
- Other names
- -
- Canonical SPDI
- NC_000015.10:45100229:T:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00008
The Genome Aggregation Database (gnomAD), exomes 0.00010
The Genome Aggregation Database (gnomAD) 0.00012
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
Trans-Omics for Precision Medicine (TOPMed) 0.00017
- Links
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 | ||
---|---|---|---|---|---|---|
HI score
Help
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. |
|||
DUOX2 | - | - |
GRCh38 GRCh37 |
1902 | 1929 |
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. |
---|---|---|---|---|
Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
May 30, 2024 | RCV001781007.4 | |
Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Apr 3, 2024 | RCV002034588.5 |
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. |
|
---|---|---|---|---|---|
Likely pathogenic
(Jan 04, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Thyroid dyshormonogenesis 6
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002789306.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Likely pathogenic
(Jan 24, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002316416.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects an acceptor splice site in intron 23 of the DUOX2 gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects an acceptor splice site in intron 23 of the DUOX2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DUOX2 are known to be pathogenic (PMID: 12110737, 18765513, 21565790, 24423310, 24735383). This variant is present in population databases (rs371960046, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DUOX2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1324302). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
|
|
Likely pathogenic
(May 30, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Thyroid dyshormonogenesis 6
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV005185270.1
First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024 |
Comment:
Variant summary: DUOX2 c.3006-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to … (more)
Variant summary: DUOX2 c.3006-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 3' acceptor site. Three predict the variant creates a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0001 in 248944 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in DUOX2 causing Thyroid Dyshormonogenesis 6, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.3006-2A>G in individuals affected with Thyroid Dyshormonogenesis 6 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1324302). Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
|
|
Likely pathogenic
(Apr 03, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV005368905.1
First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024 |
Comment:
Identified in the heterozygous state in a healthy newborn with no evidence of congenital hypothyroidism on newborn screen as part of a study of the … (more)
Identified in the heterozygous state in a healthy newborn with no evidence of congenital hypothyroidism on newborn screen as part of a study of the utility of whole genome sequencing for detection of newborn screening disorders (PMID: 26334177); Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 33651715, 34200080, 26334177) (less)
|
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 |
---|---|---|---|---|
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 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism. | Moreno JC | The New England journal of medicine | 2002 | PMID: 12110737 |
Text-mined citations for rs371960046 ...
HelpRecord last updated Oct 13, 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.