About DICER1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
DICER1 c.4199A>G, p.(Asp1400Gly)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen DICER1 VCEP v1.4.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BP4Supporting
BP4 · supporting
The DICER1 VCEP BP4_Supporting requires REVEL score <0.500 and agreement in splicing predictors that no splicing effects are predicted for missense variants. REVEL score is 0.142 (<0.500 threshold satisfied). SpliceAI max delta is 0.12, indicating no predicted splicing impact. Both conditions are met.
BP6Supporting
BP6 · supporting
Expert panel ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen classified as Likely benign.
Recorded classification: Likely benign
ClinGen DICER1 and miRNA-Processing Gene Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for DICER1 Version 1.4.0 v1.4.0 point-based framework: BP4 supporting (-1) + BP6 supporting benign (-1) = -2 points, which maps to Likely Benign.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
76 / 1,612,760 alleles
gnomAD v4.1: 76 / 1,612,760 alleles. Recorded AF 4.71242e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.79682e-05; MAF= 0.00280%, 7/250284 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 9.92457e-05; MAF= 0.00992%, 1/10076 alleles, homozygotes = 0); grpmax FAF= 1.687e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
No listed criterion applied
SpliceAI score
0.120 maximum delta
Recorded SpliceAI maximum delta score: 0.120. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
6 reported laboratory submissions
4 Uncertain significance · 2 Likely benign.
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. DICER1, an endoribonuclease, is altered in various cancer types.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen DICER1 VCEP v1.4.0, with the data and sources behind each one.
29 criteria with recorded statuses: 2 met · 16 not met · 0 not assessed · 11 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_177438.2:c.4199A>G (p.Asp1400Gly) is a missense variant in exon 22 of DICER1.
This variant is present in gnomAD v4.1 at an allele frequency of 4.71e-05 (76/1,612,760 alleles, 0 homozygotes), with a grpmax filtering allele frequency of 4.511e-05. It has been observed across multiple subpopulations, including 7 alleles in the South Asian population (AF=7.69e-05). These frequencies exceed the DICER1 VCEP PM2_Supporting threshold of <5e-06.
This variant has been reported in ClinVar as Likely Benign following review by the ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel (ClinVar Variation ID: 412173). Individual clinical laboratory submissions include Uncertain Significance (4 laboratories) and Likely Benign (2 laboratories).
In silico predictors support a benign interpretation: REVEL score is 0.142, well below the DICER1 VCEP BP4_Supporting threshold of <0.500. SpliceAI predicts no splicing impact (max delta = 0.12). These findings meet BP4_Supporting per DICER1 VCEP criteria.
The variant has been observed in two siblings with pleuropulmonary blastoma (Leckey et al. 2019, PMID:30665929). However, both siblings also carried a pathogenic DICER1 splice variant (c.2437-2A>G), and the authors explicitly state that c.4199A>G 'has not been associated with DICER1-associated phenotypic features.' In silico algorithms reportedly suggest the variant 'is likely to be tolerated.' No functional studies have been performed.
Residue Asp1400 lies outside the RNase IIIb domain (p.Y1682–S1846) and is not one of the seven metal ion-binding residues defined by the DICER1 VCEP for PM1. No pathogenic variant at the same residue is known for PS1 or PM5 application. No functional, segregation, de novo, or case-control data support application of any pathogenic criterion.
Applying the DICER1 VCEP (version 1.4.0) point-based Tavtigian framework: only BP4_Supporting (−1 point) is met. All other applicable criteria are not met. Total point value = −1, which falls within the Uncertain Significance range (Rule 3: ≥−1 and ≤5).
No criteria match.
Met · 2
BP4 SupportingThe DICER1 VCEP BP4_Supporting requires REVEL score <0.500 and agreement in splicing predictors that no splicing effects are predicted for missense variants. REVEL score is 0.142 (<0.500 threshold satisfied). SpliceAI max delta is 0.12, indicating no predicted splicing impact. Both conditions are met. Details ▾Hide ▴
Evidence considered
- REVEL 0.142 (<0.500)
- SpliceAI max delta 0.12 (no splicing impact predicted)
Sources
Not met · 16 · evaluated, threshold not reached
PS1 PS1 requires a different nucleotide change producing the same amino acid substitution (p.Asp1400Gly) that has been classified as pathogenic by the ClinGen DICER1 VCEP. No such variant is known. Details ▾Hide ▴
PS2 No de novo occurrence data are available for this variant. The DICER1 VCEP uses a de novo points system; no confirmed de novo observations with maternity and paternity confirmation have been reported. Details ▾Hide ▴
Evidence considered
- No de novo data identified in the literature or ClinVar submissions
Still missing
- No family studies with parental testing available
Sources
PS3 No functional studies (RNA splicing assay or in vitro cleavage assay) have been performed for this variant. In silico predictors (REVEL 0.142, SpliceAI max delta 0.12) suggest no deleterious splicing or functional impact. Per DICER1 VCEP, PS3 requires RNA assay demonstrating splicing impact or cleavage assay failure, neither of which is available. Details ▾Hide ▴
Evidence considered
- REVEL score 0.142 (benign range)
- SpliceAI no splicing impact
- no published functional studies per Leckey et al. 2019
Still missing
- No RNA splicing assay or in vitro cleavage assay performed
Sources
PS4 The DICER1 VCEP uses a phenotype points system for PS4. No case-control study or systematic proband collection demonstrates enrichment of this variant in affected individuals. The variant was observed in two siblings with PPB but both also carried a pathogenic DICER1 splice variant (c.2437-2A>G). Leckey et al. 2019 explicitly states the variant has not been associated with DICER1-associated phenotypic features. Details ▾Hide ▴
Evidence considered
- Observed in two siblings but co-occurring with a pathogenic DICER1 variant
- no enrichment in affected individuals demonstrated
Still missing
- No case-control or systematic proband count data
Sources
PM1 The variant results in p.Asp1400Gly. Residue 1400 is outside the RNase IIIb domain (p.Y1682–S1846) and is not one of the seven metal ion-binding residues (p.S1344, E1705, D1709, D1713, G1809, D1810, E1813) defined by the DICER1 VCEP for PM1 application. Details ▾Hide ▴
Evidence considered
- Residue D1400 is not in RNase IIIb domain or metal ion-binding sites
Sources
PM2 The DICER1 VCEP PM2_Supporting threshold is allele frequency <0.000005 across gnomAD with no more than one allele in any subpopulation. In gnomAD v4.1 (the most comprehensive version), the global allele frequency is 4.71e-05 (76/1,612,760 alleles), exceeding the PM2 threshold approximately 9-fold. The South Asian subpopulation has 7 alleles (AF=7.69e-05), which violates the 'no more than one allele in any subpopulation' requirement. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 global AF = 4.71e-05 (>5e-06)
- South Asian subpopulation 7 alleles
Sources
PM5 PM5 requires a different missense change at the same residue (D1400) that has been classified as pathogenic by the ClinGen DICER1 VCEP. No such comparator variant was identified in the PM5 candidate search. Details ▾Hide ▴
Evidence considered
- No pathogenic missense variant at residue D1400 identified
Sources
pm5_candidatescspec ↗
PP1 No co-segregation data are available for this variant. The variant was observed in two siblings but both also carry a pathogenic DICER1 splice variant (c.2437-2A>G), confounding segregation analysis. The DICER1 VCEP requires 3–4 meioses for PP1_Supporting. Details ▾Hide ▴
Evidence considered
- Observed in two siblings but co-occurring with pathogenic variant
- insufficient for segregation analysis
Still missing
- No multi-generational segregation data
Sources
PP3 The DICER1 VCEP requires REVEL score ≥0.750 for PP3_Supporting in missense variants, or agreement in splicing predictors of splicing effects. REVEL score for this variant is 0.142 (far below threshold). SpliceAI max delta is 0.12, indicating no predicted splicing impact. No evidence supports a deleterious in silico prediction. Details ▾Hide ▴
Evidence considered
- REVEL 0.142 (<0.750)
- SpliceAI max delta 0.12 (no splicing impact predicted)
Sources
PP4 The DICER1 VCEP PP4 requires somatic tumor testing demonstrating a known RNase IIIb hotspot second hit (at residues S1344, E1705, D1709, D1713, G1809, D1810, or E1813) with retention of the germline variant. No tumor testing data are available. Leckey et al. 2019 explicitly notes: 'the tumour was not tested for hotspot variants, as the family declined additional genetic testing.' Details ▾Hide ▴
Evidence considered
- No somatic tumor testing performed
- family declined additional genetic testing
Still missing
- Somatic tumor testing for RNase IIIb hotspot variants not performed
Sources
BA1 BA1 requires allele frequency >0.003 (0.3%) in a gnomAD subpopulation with >2,000 alleles tested and ≥5 alleles present. The highest subpopulation frequency in gnomAD v4.1 is South Asian at 7.69e-05 (0.0077%), far below the BA1 threshold. Details ▾Hide ▴
Evidence considered
- Highest subpopulation AF = 0.0077% (South Asian
- v4.1)
- far below 0.3% BA1 threshold
Sources
BS1 BS1 requires allele frequency >0.0003 (0.03%) in a gnomAD subpopulation with >2,000 alleles tested and ≥5 alleles present. The highest qualifying subpopulation in gnomAD v4.1 is South Asian (7 alleles, 91,066 alleles, AF=7.69e-05 = 0.0077%), which is below the BS1 threshold of 0.03%. Details ▾Hide ▴
Evidence considered
- Highest qualifying subpopulation AF = 0.0077% (South Asian v4.1)
- <0.03% BS1 threshold
Sources
BS2 BS2 requires ≥40 unrelated females tumor-free through age 50 (Strong) or ≥10 (Supporting), or homozygosity in healthy individuals. No such data are available for this variant. The gnomAD data show 76 heterozygous carriers in v4.1 but no clinical annotation of tumor status or age is available. Details ▾Hide ▴
Evidence considered
- No data on healthy adult carriers without DICER1-associated tumors
Still missing
- Lack of clinical and age data for gnomAD carriers
Sources
BS3 The DICER1 VCEP BS3_Strong requires an RNA assay showing no splicing impact (for intronic/synonymous variants) observed more than once. BS3_Supporting requires an in vitro cleavage assay demonstrating normal 5p and 3p miRNA production. Neither type of functional study has been performed for this variant. Leckey et al. 2019 notes: 'published functional studies have not been done to confirm this.' Details ▾Hide ▴
Evidence considered
- No RNA splicing assay or in vitro cleavage assay performed
- variant not functionally characterized
Still missing
- No functional studies performed
Sources
BS4 BS4 requires phenotype-positive, genotype-negative 1st–3rd degree relatives. No such family structure data are available. The only family reported (Leckey et al. 2019) shows two affected siblings both carrying the variant, which does not demonstrate lack of segregation. Details ▾Hide ▴
Evidence considered
- No non-segregation data
- both affected siblings carry the variant
Still missing
- No family data with phenotype-positive/genotype-negative relatives
Sources
BP2 BP2 requires ≥1 observation in trans with a P/LP DICER1 variant, or ≥3 observations in cis/phase unknown with 2+ different P/LP DICER1 variants. The variant co-occurs with a pathogenic DICER1 splice variant (c.2437-2A>G) in two siblings (Leckey et al. 2019), but phase is unknown. Without confirmed trans configuration, BP2 cannot be applied. Details ▾Hide ▴
Evidence considered
- Co-occurs with pathogenic c.2437-2A>G in two siblings but phase unknown
Still missing
- Parental testing needed to determine phase
Sources
Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_177438.2:c.4199A>G is a missense variant. PVS1 applies only to null variants (nonsense, frameshift, or canonical ±1,2 splice consensus). The DICER1 VCEP PVS1 decision tree does not assign PVS1 to missense substitutions. Details ▾Hide ▴
Evidence considered
- Missense variant
- not a null variant class
Sources
vcep_pvs1_decisiontree
PM3 VCEPSkipped: autosomal recessive criterion; DICER1-related tumor predisposition is autosomal dominant. Details ▾Hide ▴
No further detail was recorded.
PM4 N/ASkipped: in-frame indel criterion; not applicable to a substitution variant. Details ▾Hide ▴
No further detail was recorded.
PM6 VCEPThe DICER1 VCEP has opted to drop PM6 and exclusively use PS2 for de novo evidence. PM6 is not independently applied in this framework. Details ▾Hide ▴
PP2 VCEPThe DICER1 VCEP recommends PP2 not be used for DICER1. Although DICER1 meets the missense constraint z-score threshold (4.23 on gnomAD), the VCEP cites the presence of benign (9) and likely benign (30) missense variants throughout the gene in ClinVar as a contraindication. Details ▾Hide ▴
PP5 VCEPThe DICER1 VCEP states PP5 is not for use, per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation. Details ▾Hide ▴
BP1 VCEPThe DICER1 VCEP states: 'This rule code does not apply to this gene, as truncating variants account for only a portion of disease-causing variants.' Details ▾Hide ▴
BP3 VCEPSkipped: in-frame indels criterion; not applicable to a substitution variant. Details ▾Hide ▴
No further detail was recorded.
BP5 VCEPThe DICER1 VCEP states: 'Given the broad spectrum of DICER1-related neoplasms and the lack of evidence of other high-penetrance germline variants that could account for such neoplasms, this rule should not be used at this time.' Details ▾Hide ▴
BP7 N/ABP7 applies only to silent (synonymous) variants, intronic variants at or beyond +7/−21 positions, or other non-coding variants. NM_177438.2:c.4199A>G is a missense variant producing p.Asp1400Gly, not qualifying for BP7. Additionally, the VCEP caveat requires BP4 to be met to apply BP7. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 restricted to silent/intronic/non-coding variants
Sources
PS5 N/APS5 is not defined in the ClinGen DICER1 VCEP specification (version 1.4.0). This criterion is not part of the DICER1 gene-specific framework. Details ▾Hide ▴
Identifiers
- Gene
- DICER1
- Transcript
- NM_177438.2
- Coding (HGVS c.)
- NM_177438.2:c.4199A>G
- Protein (HGVS p.)
- NP_803187.1:p.(Asp1400Gly)
- GRCh38
- chr14:95099787 T>C
- GRCh37
- chr14:95566124 T>C
- ClinVar
- 3840003, 412173
Gene diagram
Every interpreted variant in DICER1, mapped onto the exon structure of NM_177438.2. Select a row to find it on the plot.
DICER1NM_177438.2
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in DICER1
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
76 / 1,612,760 alleles
AF 4.71e-05 · 0 homozygotes · FAF 4.51e-05
gnomAD v2.1
7 / 250,284 alleles
AF 2.8e-05 · 0 homozygotes · FAF 1.69e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 4.7e-05 · 76 / 1,612,760 alleles · 0 hom · FAF 4.5e-05
| South Asian7 / 91,066 | 7.7e-05 |
| European (non-Finnish)66 / 1,179,824 | 5.6e-05 |
| Ashkenazi Jewish1 / 29,588 | 3.4e-05 |
| Remaining individuals2 / 62,450 | 3.2e-05 |
0 alternate alleles recorded in 6 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, African/African American.
gnomAD v2.1
AF 2.8e-05 · 7 / 250,284 alleles · 0 hom · FAF 1.7e-05
| Ashkenazi Jewish1 / 10,076 | 9.9e-05 |
| European (non-Finnish)5 / 113,570 | 4.4e-05 |
| South Asian1 / 30,606 | 3.3e-05 |
0 alternate alleles recorded in 5 other groups: African/African American, Admixed American, East Asian, European (Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 4.71242e-05; MAF= 0.00471%, 76/1612760 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 7.68673e-05; MAF= 0.00769%, 7/91066 alleles, homozygotes = 0); grpmax FAF= 4.511e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.79682e-05; MAF= 0.00280%, 7/250284 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 9.92457e-05; MAF= 0.00992%, 1/10076 alleles, homozygotes = 0); grpmax FAF= 1.687e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.142
- BayesDel
- -0.084
How the predictions were used
BP4 SupportingThe DICER1 VCEP BP4_Supporting requires REVEL score <0.500 and agreement in splicing predictors that no splicing effects are predicted for missense variants. REVEL score is 0.142 (<0.500 threshold satisfied). SpliceAI max delta is 0.12, indicating no predicted splicing impact. Both conditions are met. Details ▾Hide ▴
Evidence considered
- REVEL 0.142 (<0.500)
- SpliceAI max delta 0.12 (no splicing impact predicted)
Sources
PP3 The DICER1 VCEP requires REVEL score ≥0.750 for PP3_Supporting in missense variants, or agreement in splicing predictors of splicing effects. REVEL score for this variant is 0.142 (far below threshold). SpliceAI max delta is 0.12, indicating no predicted splicing impact. No evidence supports a deleterious in silico prediction. Details ▾Hide ▴
Evidence considered
- REVEL 0.142 (<0.750)
- SpliceAI max delta 0.12 (no splicing impact predicted)
Sources
BP7 N/ABP7 applies only to silent (synonymous) variants, intronic variants at or beyond +7/−21 positions, or other non-coding variants. NM_177438.2:c.4199A>G is a missense variant producing p.Asp1400Gly, not qualifying for BP7. Additionally, the VCEP caveat requires BP4 to be met to apply BP7. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 restricted to silent/intronic/non-coding variants
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.12). REVEL score = 0.142. BayesDel score = -0.0837422.
8 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Recorded publications
-
PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Richards S et al. · 2015Landmark ACMG/AMP guidelines for sequence variant interpretation. Provides the foundational criteria framework but does not discuss the DICER1 c.4199A>G variant.Does not name this variant
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Karbassi I et al. · 2016Describes a standardized DNA variant scoring system (used by Quest Diagnostics) for Mendelian disorders. Does not mention the DICER1 c.4199A>G variant.Does not name this variant
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PMID 30665929 ↗Novel intronic DICER1 variation associated with pleuropulmonary blastoma in two siblings.Leckey BD Jr et al. · 2019Reports two siblings with pleuropulmonary blastoma carrying both a pathogenic DICER1 splice variant (c.2437-2A>G) and the c.4199A>G (p.Asp1400Gly) variant. The authors classify c.4199A>G as a variant of uncertain significance and state it has not been associated with DICER1-associated phenotypic features. In silico algorithms reportedly suggest the variant is likely to be tolerated. No functional studies were performed; tumor testing for hotspot variants was declined by the family.Names this variant
Quoted passage
In addition, the variant of uncertain significance, c.4199A>G (p.Asp1400Gly) (NM_177438.2), has been reported in the literature, but it has not been associated with DICER1-associated phenotypic features.
Outcome and follow-up section; Discussion paragraph 4
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PMID 31275557 ↗Pan-cancer repository of validated natural and cryptic mRNA splicing mutations.Shirley BC et al. · 2018Pan-cancer repository of validated splicing mutations from TCGA and ICGC datasets. Does not mention the DICER1 c.4199A>G variant.Does not name this variant
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PMID 24761742 ↗DICER1-Related Tumor Predisposition.Adam MP et al. · 1993GeneReviews entry for DICER1-Related Tumor Predisposition. Provides gene-level overview of DICER1-associated phenotypes and management but does not discuss the c.4199A>G variant.Does not name this variant
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PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015ACMG/NSGC practice guideline for cancer predisposition referral indications. Provides general referral criteria and does not discuss individual DICER1 variants.Does not name this variant
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PMID 29641532 ↗Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers.Pritchard AL et al. · 2018Germline mutation analysis in 525 cancer/DNA repair genes in 57 patients with cutaneous melanoma and at least two additional primary cancers. DICER1 was not among the genes analyzed and the variant is not mentioned.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Nykamp K et al. · 2017Sherloc variant classification refinement of ACMG/AMP guidelines. Provides a general classification framework and does not discuss this specific variant.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
76 / 1,612,760 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.120
Open source ↗
ClinVar
4 Uncertain significance · 2 Likely benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/643243094
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/412173/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/14-95566124-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr14-95099787-T-C?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/14-95099787-T-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_177438.2%3Ac.4199…
- OncoKB ↗www.oncokb.org/gene/DICER1/D1400G
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=DICER1+c.4199A%3EG
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 4.71242e-05; MAF= 0.00471%, 76/1612760 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 7.68673e-05; MAF= 0.00769%, 7/91066 alleles, homozygotes = 0); grpmax FAF= 4.511e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.79682e-05; MAF= 0.00280%, 7/250284 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 9.92457e-05; MAF= 0.00992%, 1/10076 alleles, homozygotes = 0); grpmax FAF= 1.687e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (4 clinical laboratories) and as Likely benign (2 clinical laboratories) and as Likely Benign by ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 412173)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.12). REVEL score = 0.142. BayesDel score = -0.0837422.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. DICER1, an endoribonuclease, is altered in various cancer types.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.