ClinVar Genomic variation as it relates to human health
NM_177438.3(DICER1):c.2614G>A (p.Ala872Thr)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_177438.3(DICER1):c.2614G>A (p.Ala872Thr)
Variation ID: 133967 Accession: VCV000133967.44
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 14q32.13 14: 95107916 (GRCh38) [ NCBI UCSC ] 14: 95574253 (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 9, 2014 Jun 17, 2024 May 18, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_177438.3:c.2614G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_803187.1:p.Ala872Thr missense NM_001195573.1:c.2614G>A NP_001182502.1:p.Ala872Thr missense NM_001271282.3:c.2614G>A NP_001258211.1:p.Ala872Thr missense NM_001291628.2:c.2614G>A NP_001278557.1:p.Ala872Thr missense NM_030621.4:c.2614G>A NP_085124.2:p.Ala872Thr missense NC_000014.9:g.95107916C>T NC_000014.8:g.95574253C>T NG_016311.1:g.54507G>A LRG_492:g.54507G>A LRG_492t1:c.2614G>A LRG_492p1:p.Ala872Thr - Protein change
- A872T
- Other names
- NM_177438.2(DICER1):c.2614G>A
- p.Ala872Thr
- Canonical SPDI
- NC_000014.9:95107915:C: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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0.00100 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00072
The Genome Aggregation Database (gnomAD) 0.00074
The Genome Aggregation Database (gnomAD), exomes 0.00083
Exome Aggregation Consortium (ExAC) 0.00084
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00085
1000 Genomes Project 30x 0.00094
1000 Genomes Project 0.00100
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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DICER1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
6367 | 6405 |
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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Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Aug 15, 2023 | RCV000120636.21 | |
Benign (3) |
reviewed by expert panel
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May 18, 2022 | RCV000226630.26 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Feb 24, 2020 | RCV000567312.11 | |
Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Apr 1, 2024 | RCV002227064.26 | |
DICER1-related disorder
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Likely benign (1) |
criteria provided, single submitter
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Sep 29, 2020 | RCV003925178.1 |
Benign (1) |
criteria provided, single submitter
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Jul 7, 2023 | RCV003315746.8 |
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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Benign
(May 18, 2022)
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reviewed by expert panel
Method: curation
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None
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen
FDA Recognized Database
Accession: SCV002540822.1 First in ClinVar: Jul 09, 2022 Last updated: Jul 09, 2022 |
Comment:
The NM_177438.2:c.2614G>A (p.Ala872Thr) variant in DICER1 has the highest population minor allele frequency in gnomAD v2.1.1 is 0.00119 in non-Finnish European population, which is higher … (more)
The NM_177438.2:c.2614G>A (p.Ala872Thr) variant in DICER1 has the highest population minor allele frequency in gnomAD v2.1.1 is 0.00119 in non-Finnish European population, which is higher than the ClinGen DICER1 VCEP threshold (>0.0003) for BS1, and therefore meets this criterion (BS1). This variant has been observed in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (Internal lab contributors: 61756, 500031) and has been observed in a homozygous state in 5 healthy individuals (Internal lab contributors: 26957, 500031)(BS2). In vitro cleavage assay in HEK293 cells showed that this variant produces both 5p and 3p microRNAs from a pre-miRNA, indicating that this variant is unlikely to impact protein function (PMID: 31342592)(BS3_Supporting). The computational predictor REVEL gives a score of 0.488, which is below the threshold of 0.5, and the splice site predictors MaxEntScan and SpliceAI indicate that the variant has no impact on splicing, evidence that does not predict a damaging effect on DICER1 function (BP4). In summary, this variant meets the criteria to be classified as benign for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS1, BS2, BS3_Supporting, BP4. (Bayesian Points: -10; VCEP specifications version 1; 02/11/2022). (less)
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Likely benign
(Aug 02, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000731048.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Likely benign
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002551541.4
First in ClinVar: Jul 28, 2022 Last updated: Aug 18, 2023 |
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Likely benign
(May 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004221801.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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DICER1-related tumor predisposition
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000291641.10
First in ClinVar: Jul 01, 2016 Last updated: Feb 20, 2024 |
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Likely benign
(Sep 29, 2020)
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criteria provided, single submitter
Method: clinical testing
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DICER1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004738113.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 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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Benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Pleuropulmonary blastoma
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000389755.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Likely benign
(Jul 01, 2019)
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criteria provided, single submitter
Method: curation
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Not Specified
Affected status: yes
Allele origin:
germline,
unknown
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Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research
Accession: SCV001372069.2
First in ClinVar: Jul 16, 2020 Last updated: Sep 08, 2021 |
Comment:
ACMG criteria met: PP3, BS2, BS3, BP1, BP6
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
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Likely benign
(Oct 04, 2021)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV002068612.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
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Benign
(Feb 24, 2020)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002532513.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Pleuropulmonary blastoma
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004017411.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
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Likely benign
(Nov 09, 2023)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002506106.5
First in ClinVar: May 07, 2022 Last updated: Feb 20, 2024 |
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Likely benign
(Oct 29, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000661816.5
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Likely benign
(Apr 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: SCV004130327.6
First in ClinVar: Nov 20, 2023 Last updated: Jun 17, 2024 |
Comment:
DICER1: BS1
Number of individuals with the variant: 3
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000084797.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
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Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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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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Ten years of DICER1 mutations: Provenance, distribution, and associated phenotypes. | de Kock L | Human mutation | 2019 | PMID: 31342592 |
Sequencing of DICER1 in sarcomas identifies biallelic somatic DICER1 mutations in an adult-onset embryonal rhabdomyosarcoma. | de Kock L | British journal of cancer | 2017 | PMID: 28524158 |
Germ-line variants identified by next generation sequencing in a panel of estrogen and cancer associated genes correlate with poor clinical outcome in Lynch syndrome patients. | Jóri B | Oncotarget | 2015 | PMID: 26517685 |
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. | Bodian DL | PloS one | 2014 | PMID: 24728327 |
DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma. | Doros LA | Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc | 2014 | PMID: 24481001 |
Biallelic DICER1 mutations occur in Wilms tumours. | Wu MK | The Journal of pathology | 2013 | PMID: 23620094 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/d0180ab5-21d7-45b9-bb2f-91f305099d4f | - | - | - | - |
Text-mined citations for rs149242330 ...
HelpRecord last updated Jun 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.