About DICER1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
DICER1 c.2997T>G, p.(Leu999=)
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A 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: 5
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 5
BA1Stand alone
BA1 · stand alone
NM_177438.3:c.2997T>G has an allele frequency of 5.69% in the African/African American population in gnomAD v4.1 (4272/75026 alleles, 116 homozygotes), exceeding the DICER1 VCEP BA1 threshold of >0.3% in a subpopulation with >2000 alleles and ≥5 alleles present. This frequency is incompatible with a highly penetrant autosomal dominant tumor predisposition syndrome.
BS1Strong
BS1 · strong
The African/African American subpopulation AF of 5.69% in gnomAD v4.1 exceeds the DICER1 VCEP BS1 threshold of >0.03% with >2000 alleles and ≥5 alleles present. This criterion is independently met but subsumed by BA1.
BS2Supporting
BS2 · supporting
Per DICER1 VCEP BS2_Supporting: '2+ observations of homozygosity in individuals lacking clinical information.' gnomAD v4.1 reports 121 homozygotes for NM_177438.3:c.2997T>G. The presence of numerous homozygous individuals in a population database is inconsistent with a pathogenic dominant tumor predisposition variant.
BP4Supporting
BP4 · supporting
Per DICER1 VCEP: for synonymous variants, concordance of MaxEntScan and SpliceAI showing no splicing effects qualifies for BP4_Supporting. SpliceAI predicts no splicing impact (max delta score = 0.03). This synonymous change at c.2997T>G is not predicted to create a cryptic splice site or disrupt splicing.
BP7Supporting
BP7 · supporting
NM_177438.3:c.2997T>G is a synonymous (silent) variant (p.Leu999=). Per DICER1 VCEP BP7_Supporting: 'Silent variant... Caveat: Variant must meet BP4 to apply BP7.' BP4 is met (SpliceAI predicts no splicing impact, delta = 0.03). This variant does not alter the amino acid sequence and is not predicted to affect splicing.
Recorded classification: 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: BA1 stand-alone benign (-8) + BS1 strong benign (-4) + BS2 supporting benign (-1) + BP4 supporting benign (-1) + BP7 supporting benign (-1) = -15 points, which maps to 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
5,007 / 1,613,832 alleles
gnomAD v4.1: 5,007 / 1,613,832 alleles. Recorded AF 0.00310255. Recorded homozygote count 121.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00563595; MAF= 0.56359%, 1593/282650 alleles, homozygotes = 38) and has highest observed frequency in the African/African American population (AF= 0.05716; MAF= 5.71600%, 1425/24930 alleles, homozygotes = 38); grpmax FAF= 0.0559887.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0036377456835704203, 67/18418 alleles, homozygotes = 0).
SpliceAI score
0.030 maximum delta
Recorded SpliceAI maximum delta score: 0.030. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
10 reported laboratory submissions
9 Benign · 1 benign.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
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.
26 criteria with recorded statuses: 5 met · 8 not met · 0 not assessed · 13 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_177438.3:c.2997T>G (p.Leu999=) is a synonymous variant in exon 19 of DICER1. It is present at high frequency in gnomAD v4.1 with an overall allele frequency of 0.31% (5007/1613832 alleles) and 121 homozygotes. The highest subpopulation frequency is 5.69% in African/African American individuals (4272/75026 alleles, 116 homozygotes), exceeding the VCEP BA1 stand-alone benign threshold of >0.3%.
BA1 (Stand-Alone Benign) is met: the African/African American subpopulation allele frequency of 5.69% exceeds the 0.3% threshold with >2000 alleles tested and ≥5 alleles present. A frequency of this magnitude is incompatible with a highly penetrant autosomal dominant tumor predisposition disorder.
BS1 (Strong Benign) is independently met at the >0.03% threshold in the same subpopulation, subsumed by the stronger BA1 evidence.
BS2_Supporting is met: 121 homozygous individuals are reported in gnomAD v4.1, satisfying the VCEP threshold of ≥2 homozygotes in individuals lacking clinical information.
BP4_Supporting is met: SpliceAI predicts no splicing impact for this synonymous variant (max delta score = 0.03).
BP7_Supporting is met: the variant is a synonymous change (p.Leu999=) and meets BP4, satisfying the DICER1 VCEP BP7 requirements.
This variant has been classified as Benign by 10 clinical laboratories in ClinVar (VariationID: 261920), consistent with the population frequency evidence.
No publications among the seven reviewed (PMID:25741868, 26467025, 24493721, 29474644, 24761742, 25394175, 28492532) specifically mention NM_177438.3:c.2997T>G or p.Leu999=. All are methodology, guideline, or gene-level review papers without variant-specific evidence.
Under the Tavtigian point-based system (DICER1 VCEP v1.4.0): BA1 = -8 points. BS2_Supporting = -1 point. BP4_Supporting = -1 point. BP7_Supporting = -1 point. Total = -11 points. Classification: Benign (≤ -7).
No criteria match.
Met · 5
BA1 Stand aloneNM_177438.3:c.2997T>G has an allele frequency of 5.69% in the African/African American population in gnomAD v4.1 (4272/75026 alleles, 116 homozygotes), exceeding the DICER1 VCEP BA1 threshold of >0.3% in a subpopulation with >2000 alleles and ≥5 alleles present. This frequency is incompatible with a highly penetrant autosomal dominant tumor predisposition syndrome. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 African/African American AF = 5.69% (4272/75026 alleles
- 116 homozygotes)
- gnomAD v2.1 African/African American AF = 5.72% (1425/24930 alleles
- 38 homozygotes).
Sources
BS1 StrongThe African/African American subpopulation AF of 5.69% in gnomAD v4.1 exceeds the DICER1 VCEP BS1 threshold of >0.03% with >2000 alleles and ≥5 alleles present. This criterion is independently met but subsumed by BA1. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 African/African American AF = 5.69% exceeds BS1 threshold of 0.03%.
Sources
BS2 SupportingPer DICER1 VCEP BS2_Supporting: '2+ observations of homozygosity in individuals lacking clinical information.' gnomAD v4.1 reports 121 homozygotes for NM_177438.3:c.2997T>G. The presence of numerous homozygous individuals in a population database is inconsistent with a pathogenic dominant tumor predisposition variant. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 121 homozygotes
- gnomAD v2.1: 38 homozygotes.
Still missing
- Homozygote clinical phenotype data not available
- derived from population controls.
Sources
BP4 SupportingPer DICER1 VCEP: for synonymous variants, concordance of MaxEntScan and SpliceAI showing no splicing effects qualifies for BP4_Supporting. SpliceAI predicts no splicing impact (max delta score = 0.03). This synonymous change at c.2997T>G is not predicted to create a cryptic splice site or disrupt splicing. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.03
- no predicted splicing alteration for this synonymous variant.
Still missing
- MaxEntScan score not independently verified
- SpliceAI prediction alone used for BP4 determination.
Sources
BP7 SupportingNM_177438.3:c.2997T>G is a synonymous (silent) variant (p.Leu999=). Per DICER1 VCEP BP7_Supporting: 'Silent variant... Caveat: Variant must meet BP4 to apply BP7.' BP4 is met (SpliceAI predicts no splicing impact, delta = 0.03). This variant does not alter the amino acid sequence and is not predicted to affect splicing. Details ▾Hide ▴
Evidence considered
- Synonymous variant p.(Leu999=)
- SpliceAI delta = 0.03 (no splicing effect)
- BP4 met.
Still missing
- Nucleotide conservation status not formally assessed
- high population frequency and homozygote count argue against stringent conservation.
Sources
Not met · 8 · evaluated, threshold not reached
PS2 No de novo observations identified for NM_177438.3:c.2997T>G in any reviewed publication or ClinVar submission. The variant is common in population databases (gnomAD homozygote count = 121 in v4.1), which is inconsistent with a highly penetrant de novo variant. Details ▾Hide ▴
Evidence considered
- 121 homozygotes in gnomAD v4.1 argue against a de novo disease-causing role.
Still missing
- No de novo case reports identified.
Sources
PS3 No well-established in vitro or in vivo functional studies (RNA splicing assay or cleavage assay) have been performed for this specific variant. The reviewed publications are methodology or guideline papers that do not report functional data for NM_177438.3:c.2997T>G. Details ▾Hide ▴
Evidence considered
- No variant-specific functional studies identified in the literature or databases.
Still missing
- No RNA assay or in vitro cleavage data available for this variant.
PM2 Per DICER1 VCEP: PM2_Supporting requires allele frequency <0.000005 across gnomAD. This variant has AF = 0.00310 (0.31%) in gnomAD v4.1 and AF = 0.00564 (0.56%) in gnomAD v2.1, far exceeding the threshold. Highest subpopulation AF = 5.69% (African/African American, gnomAD v4.1). Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 AF=0.31% (5007/1613832 alleles)
- gnomAD v2.1 AF=0.56% (1593/282650 alleles). Threshold is 0.0005%.
Sources
PP3 Per DICER1 VCEP: PP3_Supporting requires REVEL ≥ 0.750 for missense variants OR agreement in splicing predictors predicting splicing effects. This variant is synonymous (REVEL not applicable) and SpliceAI max delta = 0.03 predicts no splicing impact. No evidence of a deleterious effect on the gene product. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.03 (no predicted splicing impact)
- REVEL not applicable to synonymous variants.
Still missing
- MaxEntScan score not independently available for splicing concordance check.
Sources
PP4 No somatic tumor testing data available demonstrating a DICER1 somatic hotspot second hit (at p.S1344, p.E1705, p.D1709, p.D1713, p.G1809, p.D1810, or p.E1813) with retention of the germline variant. No tumor sequencing data identified. Details ▾Hide ▴
Evidence considered
- No tumor testing or somatic second-hit data available for this variant.
Still missing
- No somatic tumor sequencing data available.
BS3 Per DICER1 VCEP BS3_Strong: requires 'no splicing impact observed via RNA assay (observed more than once).' No RNA assay data is available for this variant. SpliceAI predicts no splicing effect (delta = 0.03) but this is in silico prediction, not functional RNA data. BS3_Supporting requires a cleavage assay demonstrating normal microRNA production, which has not been performed. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.03 (no predicted splicing impact)
- but no confirmatory RNA assay data available.
Still missing
- No RNA splicing assay performed
- no in vitro cleavage assay data.
Sources
BS4 No segregation data available. No evidence of phenotype-positive, genotype-negative first-, second-, or third-degree relatives of a proband carrying this variant. Details ▾Hide ▴
Evidence considered
- No family segregation data identified.
Still missing
- No family studies or segregation data available.
BP2 No observations of NM_177438.3:c.2997T>G in trans with a pathogenic/likely pathogenic DICER1 variant, nor in cis with 2+ different P/LP DICER1 variants, in any reviewed data source. Details ▾Hide ▴
Evidence considered
- No trans or cis observations with P/LP DICER1 variants identified.
Still missing
- No phase data available for this variant.
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_177438.3:c.2997T>G is a synonymous variant (p.Leu999=) in exon 19. VCEP PVS1 applies only to null variants (nonsense, frameshift, canonical splice ±1,2, initiation codon, exon deletion). This variant does not alter the amino acid sequence and is not a null variant. Details ▾Hide ▴
Evidence considered
- Synonymous variant p.(Leu999=)
- not a null variant class eligible for PVS1.
Sources
pvs1_variant_assessmentcspec ↗
PS1 N/APS1 requires the same amino acid change as a previously established pathogenic missense variant. This is a synonymous variant (p.Leu999=) with no amino acid change; there is no comparator pathogenic missense at this codon under the VCEP rule. Details ▾Hide ▴
PS4 N/APer DICER1 VCEP v1.4.0: 'Do not apply PS4 if variant meets BA1/BS1 criteria.' BA1 and BS1 are both met (African/African American AF = 5.69% in gnomAD v4.1). The variant is too common in the general population for PS4 to be applicable. Details ▾Hide ▴
PM1 N/APM1 applies to missense variants at specific functional residues (metal ion-binding codons p.S1344, p.E1705, p.D1709, p.D1713, p.G1809, p.D1810, p.E1813 for moderate; RNase IIIb domain for supporting). This is a synonymous variant, not a missense change. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- PM1 requires a missense change at defined hotspot residues.
Sources
PM5 N/APM5 requires a missense variant at a residue where a different pathogenic missense has been observed. This is a synonymous variant (p.Leu999=) with no amino acid change. Per pm5_candidates.json: 'Framework is classic same-residue missense PM5, but the variant class is not missense-like.' Details ▾Hide ▴
Evidence considered
- Synonymous variant not eligible for missense-based PM5 comparison.
Sources
pm5_candidatescspec ↗
PM6 VCEPPer DICER1 VCEP v1.4.0: PM6 is Not Applicable. The VCEP has combined PM6 with PS2 and uses PS2 exclusively for de novo evidence. Details ▾Hide ▴
PP1 N/APer DICER1 VCEP v1.4.0: 'Do not apply PP1 if variant meets BA1/BS1 criteria.' BA1 and BS1 are both met. Segregation analysis is contraindicated for a variant this common in the general population. Details ▾Hide ▴
PP2 VCEPPer DICER1 VCEP v1.4.0: PP2 is Not Applicable. The VCEP states: 'While DICER1 does meet recommended cutoff for missense constraint z score... the VCEP recommends this rule not be used for DICER1 due to the presence of various missense variants throughout the gene that are clinically interpreted as benign or likely benign in ClinVar.' Details ▾Hide ▴
PP5 VCEPPer DICER1 VCEP v1.4.0: PP5 is Not Applicable. 'This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.' Details ▾Hide ▴
BP1 VCEPPer DICER1 VCEP v1.4.0: BP1 is Not Applicable. The 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 ▴
BP5 VCEPPer DICER1 VCEP v1.4.0: BP5 is Not Applicable. The 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 ▴
BP6 VCEPPer DICER1 VCEP v1.4.0: BP6 is Not Applicable. 'This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.' Details ▾Hide ▴
PS5 N/APS5 is not a criterion defined by the DICER1 VCEP v1.4.0 nor by standard ACMG/AMP 2015 guidelines. This criterion code is not in use. Details ▾Hide ▴
Evidence considered
- PS5 is not a recognized ACMG/AMP criterion.
Identifiers
- Gene
- DICER1
- Transcript
- NM_177438.3
- Coding (HGVS c.)
- NM_177438.3:c.2997T>G
- Protein (HGVS p.)
- NP_803187.1:p.(Leu999=)
- GRCh38
- chr14:95105774 A>C
- GRCh37
- chr14:95572111 A>C
- ClinVar
- 261920
Gene diagram
Every interpreted variant in DICER1, mapped onto the exon structure of NM_177438.3. Select a row to find it on the plot.
DICER1NM_177438.3
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
5,007 / 1,613,832 alleles
AF 0.0031 · 121 homozygotes · FAF 0.0555
gnomAD v2.1
1,593 / 282,650 alleles
AF 0.00564 · 38 homozygotes · FAF 0.056
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.0031 · 5007 / 1,613,832 alleles · 121 hom · FAF 0.056
| African/African American4272 / 75,026 | 0.057116 hom |
| Remaining individuals259 / 62,496 | 0.00414 hom |
| Admixed American233 / 60,030 | 0.0039 |
| Middle Eastern20 / 6,060 | 0.00331 hom |
| European (non-Finnish)216 / 1,179,712 | 0.00018 |
| South Asian7 / 91,072 | 7.7e-05 |
0 alternate alleles recorded in 4 other groups: European (Finnish), Amish, East Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 0.0056 · 1593 / 282,650 alleles · 38 hom · FAF 0.056
| African/African American1425 / 24,930 | 0.05738 hom |
| Admixed American109 / 35,434 | 0.0031 |
| Remaining individuals17 / 7,208 | 0.0024 |
| European (non-Finnish)40 / 129,032 | 0.00031 |
| South Asian2 / 30,606 | 6.5e-05 |
0 alternate alleles recorded in 3 other groups: Ashkenazi Jewish, East Asian, European (Finnish).
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.00310255; MAF= 0.31026%, 5007/1613832 alleles, homozygotes = 121) and has highest observed frequency in the African/African American population (AF= 0.0569403; MAF= 5.69403%, 4272/75026 alleles, homozygotes = 116); grpmax FAF= 0.0555142.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00563595; MAF= 0.56359%, 1593/282650 alleles, homozygotes = 38) and has highest observed frequency in the African/African American population (AF= 0.05716; MAF= 5.71600%, 1425/24930 alleles, homozygotes = 38); grpmax FAF= 0.0559887.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0036377456835704203, 67/18418 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingPer DICER1 VCEP: for synonymous variants, concordance of MaxEntScan and SpliceAI showing no splicing effects qualifies for BP4_Supporting. SpliceAI predicts no splicing impact (max delta score = 0.03). This synonymous change at c.2997T>G is not predicted to create a cryptic splice site or disrupt splicing. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.03
- no predicted splicing alteration for this synonymous variant.
Still missing
- MaxEntScan score not independently verified
- SpliceAI prediction alone used for BP4 determination.
Sources
BP7 SupportingNM_177438.3:c.2997T>G is a synonymous (silent) variant (p.Leu999=). Per DICER1 VCEP BP7_Supporting: 'Silent variant... Caveat: Variant must meet BP4 to apply BP7.' BP4 is met (SpliceAI predicts no splicing impact, delta = 0.03). This variant does not alter the amino acid sequence and is not predicted to affect splicing. Details ▾Hide ▴
Evidence considered
- Synonymous variant p.(Leu999=)
- SpliceAI delta = 0.03 (no splicing effect)
- BP4 met.
Still missing
- Nucleotide conservation status not formally assessed
- high population frequency and homozygote count argue against stringent conservation.
Sources
PP3 Per DICER1 VCEP: PP3_Supporting requires REVEL ≥ 0.750 for missense variants OR agreement in splicing predictors predicting splicing effects. This variant is synonymous (REVEL not applicable) and SpliceAI max delta = 0.03 predicts no splicing impact. No evidence of a deleterious effect on the gene product. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.03 (no predicted splicing impact)
- REVEL not applicable to synonymous variants.
Still missing
- MaxEntScan score not independently available for splicing concordance check.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03).
7 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
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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. · 2015ACMG/AMP standards and guidelines for sequence variant interpretation. This methods paper establishes the framework for variant classification but does not discuss individual variants or genes.Does not name this variant
-
PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Karbassi I et al. · 2016A standardized DNA variant scoring system for Mendelian disorders (Karbassi et al.). Describes a computational scoring methodology for variant classification. Does not discuss NM_177438.3:c.2997T>G or DICER1 specifically.Does not name this variant
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PMID 29474644 ↗DICER1 Mutations Are Frequent in Adolescent-Onset Papillary Thyroid Carcinoma.Wasserman JD et al. · 2018DICER1 mutations are frequent in adolescent-onset papillary thyroid carcinoma (Wasserman et al., 2018). Reports DICER1 somatic and germline variants in pediatric PTC but does not mention c.2997T>G or p.Leu999=.Does not name this variant
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PMID 24493721 ↗American Society of Clinical Oncology Expert Statement: collection and use of a cancer family history for oncology providers.Lu KH et al. · 2014ASCO expert statement on collection and use of cancer family history for oncology providers. A clinical practice guideline with no discussion of individual variants or DICER1.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. A general clinical overview of the gene and associated phenotypes.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 on referral indications for cancer predisposition assessment. A clinical guideline with no individual variant discussion.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: a comprehensive refinement of ACMG-AMP variant classification criteria (Nykamp et al., 2017). A classification framework paper that does not discuss specific DICER1 variants.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
5,007 / 1,613,832 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.030
Open source ↗
ClinVar
9 Benign · 1 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/261920/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/14-95572111-A-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr14-95105774-A-C?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/14-95105774-A-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_177438.3%3Ac.2997…
- OncoKB ↗www.oncokb.org/gene/DICER1/L999=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=DICER1+c.2997T%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= 0.00310255; MAF= 0.31026%, 5007/1613832 alleles, homozygotes = 121) and has highest observed frequency in the African/African American population (AF= 0.0569403; MAF= 5.69403%, 4272/75026 alleles, homozygotes = 116); grpmax FAF= 0.0555142.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00563595; MAF= 0.56359%, 1593/282650 alleles, homozygotes = 38) and has highest observed frequency in the African/African American population (AF= 0.05716; MAF= 5.71600%, 1425/24930 alleles, homozygotes = 38); grpmax FAF= 0.0559887.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0036377456835704203, 67/18418 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Benign (9 clinical laboratories) and as benign (1 clinical laboratory). (ClinVarID = 261920)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03).
Functional
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
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.