About DICER1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
DICER1 c.3334A>G, p.(Asn1112Asp)
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. 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
BS1Strong
BS1 · strong
The East Asian population allele frequency of 0.098% (gnomAD v2.1, 18/18,382 alleles) and 0.198% (gnomAD v4.1, 89/44,880 alleles) exceeds the DICER1 VCEP BS1 threshold of >0.03%. The subpopulation has >2,000 alleles tested and >5 alleles present, satisfying all BS1 requirements at strong strength.
BP4Supporting
BP4 · supporting
REVEL score of 0.109 is well below the DICER1 VCEP BP4 threshold of <0.500, and SpliceAI predicts no splicing impact (max delta score 0.09). The agreement of multiple in silico predictors supports a benign interpretation.
Recorded classification: Likely benign
DICER1 VCEP v1.4 Tavtigian point-based framework applied to adjudicated criteria: BS1_Strong (-4 points) + BP4_Supporting (-1 point) = -5 points. Per the VCEP point rules, -5 falls within the Likely Benign range (>= -6 and <= -2). The special override for -1 (>=2 benign codes with only PM2_Supporting pathogenic) does not apply since the score is -5.
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
90 / 1,614,090 alleles
gnomAD v4.1: 90 / 1,614,090 alleles. Recorded AF 5.5759e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.17755e-05; MAF= 0.00718%, 18/250782 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000979219; MAF= 0.09792%, 18/18382 alleles, homozygotes = 0); grpmax FAF= 0.0006324.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.090 maximum delta
Recorded SpliceAI maximum delta score: 0.090. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
4 reported laboratory submissions
3 Likely benign · 1 Uncertain significance. ClinVar API review status: criteria provided, conflicting classifications.
Context only
ClinVar ↗
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
3 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV58626859, n = 3 times).
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, 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.3334A>G (p.Asn1112Asp) is a missense variant in exon 21 of DICER1, located outside the RNase IIIb catalytic domain (p.Y1682-p.S1846) and not at a metal ion-binding residue.
This variant is present in gnomAD at a frequency exceeding the DICER1 VCEP threshold for rarity. In the East Asian population, the allele frequency is 0.098% (gnomAD v2.1, 18/18,382 alleles) and 0.198% (gnomAD v4.1, 89/44,880 alleles), meeting BS1 at strong strength (VCEP threshold: >0.03%).
Computational predictions uniformly support a benign interpretation: REVEL score 0.109 (below BP4 threshold of <0.500), SpliceAI max delta 0.09 (no splicing impact), and BayesDel score -0.562 (benign). BP4 is met at supporting strength.
In ClinVar, this variant has been classified as Likely benign by three clinical laboratories (Ambry Genetics, Labcorp/Invitae, Illumina) and as Uncertain significance by one (GeneDx). No expert panel has reviewed this variant. The ITMI submission derived from a reference population cohort (Bodian et al. 2014), consistent with a benign population variant.
No functional studies, segregation data, de novo observations, or tumor testing data are available for this variant. No pathogenic comparator variants exist at codon 1112 for PM5 application. The variant falls outside characterized functional domains, so PM1 does not apply.
Applying the DICER1 VCEP v1.4 Tavtigian point-based classification framework: BS1_Strong (-4 points) + BP4_Supporting (-1 point) = -5 points. This falls within the Likely Benign range (>= -6 and <= -2).
Final classification: Likely Benign.
No criteria match.
Met · 2
BS1 StrongThe East Asian population allele frequency of 0.098% (gnomAD v2.1, 18/18,382 alleles) and 0.198% (gnomAD v4.1, 89/44,880 alleles) exceeds the DICER1 VCEP BS1 threshold of >0.03%. The subpopulation has >2,000 alleles tested and >5 alleles present, satisfying all BS1 requirements at strong strength. Details ▾Hide ▴
Evidence considered
- EAS AF 0.098% (v2.1
- 18/18382)
- 0.198% (v4.1
- 89/44880)
- exceeds VCEP BS1 threshold of 0.03% in a qualifying subpopulation.
Sources
BP4 SupportingREVEL score of 0.109 is well below the DICER1 VCEP BP4 threshold of <0.500, and SpliceAI predicts no splicing impact (max delta score 0.09). The agreement of multiple in silico predictors supports a benign interpretation. Details ▾Hide ▴
Evidence considered
- REVEL 0.109 (<0.500 BP4 threshold)
- SpliceAI max delta 0.09 (no splicing effect)
- BayesDel -0.562 (benign).
Sources
Not met · 16 · evaluated, threshold not reached
PS1 No different nucleotide change at c.3334 resulting in the same amino acid change (p.Asn1112Asp) has been classified as pathogenic by the ClinGen DICER1 VCEP. Per VCEP rules, PS1 requires a comparator variant asserted as pathogenic by the DICER1 VCEP at the same amino acid position. Details ▾Hide ▴
PS2 No de novo observations have been reported for NM_177438.2:c.3334A>G (p.Asn1112Asp). The DICER1 VCEP requires de novo points tallied from confirmed de novo events with DICER1-related phenotypes; none are available. Details ▾Hide ▴
Evidence considered
- No de novo reports identified in ClinVar submissions or literature.
Still missing
- No de novo analysis has been performed for this variant.
PS3 No functional studies (RNA splicing assay or in vitro cleavage assay) have been reported for p.Asn1112Asp. Computationally, REVEL score 0.109 and SpliceAI max delta 0.09 do not predict a deleterious effect. N1112 is outside the RNase IIIb catalytic domain and is not a metal ion-binding residue. No experimental evidence supports a damaging effect on DICER1 function. Details ▾Hide ▴
Evidence considered
- REVEL 0.109
- BayesDel -0.562
- SpliceAI max delta 0.09
- variant not in a characterized functional domain (outside RNase IIIb Y1682-S1846)
- no RNA or cleavage assay data available.
Still missing
- No variant-specific functional studies performed.
Sources
PS4 No probands with DICER1-related tumor predisposition phenotypes have been reported to carry this variant. The variant has been observed in ClinVar with 3 clinical laboratories classifying it as Likely benign and 1 as Uncertain significance. The Bodian et al. 2014 cohort (PMID:24728327) identified this variant in a healthy population screen, consistent with a benign interpretation rather than enrichment in affected individuals. The ITMI submission also derives from a reference population. No phenotype points can be assigned under the DICER1 VCEP PS4 rubric. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Likely benign (3 labs)
- VUS (1 lab)
- variant observed in healthy population cohort (Bodian et al. 2014)
- no DICER1-phenotype probands reported.
Sources
PM1 p.Asn1112 is not located within the RNase IIIb domain (p.Y1682-p.S1846) and is not one of the seven metal ion-binding hotspot residues (p.S1344, p.E1705, p.D1709, p.D1713, p.G1809, p.D1810, p.E1813) per the DICER1 VCEP PM1 specification. The variant lies in a region with no known critical functional domain. Details ▾Hide ▴
Evidence considered
- N1112 is outside the RNase IIIb domain (Y1682-S1846)
- not a metal ion-binding residue
- no cancerhotspots.org significance.
Sources
PM2 This variant is present in gnomAD v2.1 at an overall allele frequency of 0.00718% (18/250,782 alleles) and gnomAD v4.1 at 0.00558% (90/1,614,090 alleles), both exceeding the DICER1 VCEP PM2_Supporting threshold of <0.0005%. The East Asian subpopulation has 18 alleles in v2.1 and 89 in v4.1, far exceeding the 'no more than one allele in any subpopulation' requirement. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.00718% (18/250782)
- v4.1 AF=0.00558% (90/1614090)
- EAS subpopulation 18-89 alleles
- exceeds VCEP PM2 threshold of <0.0005% and >1 allele rule.
Sources
PM5 No pathogenic missense variant at codon 1112 has been classified by the ClinGen DICER1 VCEP for comparison. The PM5 candidates search returned zero same-residue comparator variants. Per VCEP PM5 rules, a comparator must be interpreted as pathogenic by the DICER1 VCEP with equal or worse Grantham score, which cannot be satisfied without an eligible comparator. Details ▾Hide ▴
Evidence considered
- No same-residue pathogenic comparator classified by DICER1 VCEP available at codon 1112.
Sources
pm5_candidatescspec ↗
PP1 No co-segregation data are available for this variant. No family studies reporting segregation of p.Asn1112Asp with DICER1-related phenotypes have been identified in the literature or ClinVar submissions. Details ▾Hide ▴
Evidence considered
- No segregation data available.
Still missing
- No family studies have been conducted for this variant.
PP3 REVEL score of 0.109 is well below the DICER1 VCEP PP3 threshold of >=0.750. SpliceAI predicts no splicing impact (max delta 0.09). BayesDel score of -0.562 corroborates a benign prediction. Multiple computational lines of evidence suggest no deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL 0.109 (<0.750 threshold)
- SpliceAI max delta 0.09 (no splicing effect)
- BayesDel -0.562 (benign prediction).
Sources
PP4 No somatic tumor testing data are available for a proband carrying this germline variant. The DICER1 VCEP PP4 rule requires demonstration of a somatic second hit at a known RNase IIIb hotspot codon (p.S1344, p.E1705, p.D1709, p.D1713, p.G1809, p.D1810, or p.E1813) with retention of the germline variant. Such data are absent. Details ▾Hide ▴
Evidence considered
- No tumor testing data available.
Still missing
- No somatic tumor testing has been performed on a carrier of this variant.
BA1 The highest subpopulation allele frequency is in East Asians at 0.098% (gnomAD v2.1, 18/18,382 alleles) and 0.198% (gnomAD v4.1, 89/44,880 alleles), both below the DICER1 VCEP BA1 threshold of >0.3%. While the Korean sub-subpopulation (EAS_KOR) reaches 0.394% in v2.1, the VCEP typically evaluates major continental subpopulations. Using the most comprehensive gnomAD version (v4.1), the EAS frequency remains below the BA1 cutoff. Details ▾Hide ▴
Evidence considered
- EAS AF 0.098% (v2.1)
- 0.198% (v4.1)
- both below BA1 threshold of 0.3%.
Sources
BS2 No data are available on healthy adult carriers meeting the DICER1 VCEP BS2 criteria. The variant has been observed in gnomAD in heterozygous state (0 homozygotes), but no study has specifically documented 40+ unrelated tumor-free females through age 50, nor are there confirmed homozygous healthy individuals. Details ▾Hide ▴
Evidence considered
- Variant observed in gnomAD (0 homozygotes)
- no dedicated healthy-adult carrier study meeting VCEP BS2 thresholds.
Still missing
- No study specifically documenting healthy adult carriers.
Sources
BS3 No functional studies demonstrating no damaging effect on DICER1 splicing or pre-miRNA cleavage have been performed for p.Asn1112Asp. The DICER1 VCEP BS3 rule requires RNA assay data (no splicing impact, observed more than once) or in vitro cleavage assay showing normal 5p/3p miRNA production. Neither is available. Computational predictions alone (REVEL 0.109, SpliceAI max delta 0.09) do not satisfy BS3 which requires experimental functional evidence. Details ▾Hide ▴
Evidence considered
- No RNA assay or cleavage assay data available
- computational predictions alone insufficient for BS3 per VCEP.
Still missing
- No experimental functional studies performed.
Sources
revelspliceai ↗
BS4 No family segregation data are available for this variant. BS4 under the DICER1 VCEP requires phenotype-positive, genotype-negative 1st/2nd/3rd degree relatives with high- or moderate-specificity phenotypes. No such data have been reported. Details ▾Hide ▴
Evidence considered
- No family segregation studies available.
Still missing
- No family segregation data.
BP2 No observations of this variant in trans with a P/LP DICER1 variant have been reported. The DICER1 VCEP BP2 rule requires at least one observation in trans with a P/LP DICER1 variant (or >=3 in cis/phase unknown with 2+ different P/LP variants). No such data exist. Details ▾Hide ▴
Evidence considered
- No trans/cis observations with P/LP DICER1 variants.
Still missing
- No phase data available.
PS5 PS5 is not included in the DICER1 VCEP criteria specification. Even under generic ACMG/AMP, PS5 would require a reputable source to have recently reported the variant as pathogenic with evidence unavailable for independent evaluation; ClinVar reports this variant as Likely benign, not pathogenic. Details ▾Hide ▴
Evidence considered
- ClinVar consensus is Likely benign
- not pathogenic
- no reputable source has classified this variant as pathogenic.
Sources
Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_177438.2:c.3334A>G is a missense variant (p.Asn1112Asp), not a null variant (nonsense, frameshift, or canonical splice). The DICER1 VCEP PVS1 rules apply exclusively to nonsense, frameshift, and canonical splice variants. Missense variants do not qualify for PVS1. Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution
- not a null variant
- PVS1 not applicable per DICER1 VCEP rules.
Sources
PM3 VCEPDICER1-related tumor predisposition is autosomal dominant; PM3 applies to recessive disorders only. Details ▾Hide ▴
No further detail was recorded.
PM4 N/AMissense substitution; PM4 applies only to in-frame deletions/insertions and stop-loss variants. Details ▾Hide ▴
No further detail was recorded.
PM6 VCEPPM6 is combined with PS2 per the DICER1 VCEP specification; the expert panel has opted to drop PM6 and exclusively use PS2 for de novo evidence. Assessed under PS2 instead. Details ▾Hide ▴
PP2 VCEPPP2 is not applicable per the DICER1 VCEP. Despite DICER1 meeting the missense constraint Z-score cutoff (4.23 on gnomAD), the VCEP recommends this rule not be used due to the presence of numerous missense variants throughout the gene clinically interpreted as benign (9) or likely benign (30) in ClinVar. Details ▾Hide ▴
PP5 VCEPPP5 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee per the DICER1 VCEP specification. Even under generic ACMG/AMP, this variant is classified as Likely benign by multiple clinical laboratories, not pathogenic. Details ▾Hide ▴
BP1 VCEPBP1 is not applicable per the DICER1 VCEP. Truncating variants account for only a portion of disease-causing variants in DICER1, and missense variants (particularly in the RNase IIIb domain) are an established disease mechanism. Details ▾Hide ▴
BP3 VCEPMissense substitution; BP3 applies only to in-frame deletions/insertions in repetitive regions without known function. Details ▾Hide ▴
No further detail was recorded.
BP5 VCEPBP5 is not applicable per the DICER1 VCEP. 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, the VCEP recommends this rule not be used at this time. Details ▾Hide ▴
BP6 VCEPBP6 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee per the DICER1 VCEP specification. Details ▾Hide ▴
BP7 N/ABP7 applies only to silent (synonymous) variants, deep intronic variants (at or beyond +7/-21 positions), or non-coding variants where the reference nucleotide is conserved across >=1 primate and/or >=4 mammalian species. NM_177438.2:c.3334A>G is a missense variant (p.Asn1112Asp) and does not meet any BP7 eligibility criteria. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is for silent/intronic/non-coding variants only.
Sources
Identifiers
- Gene
- DICER1
- Transcript
- NM_177438.2
- Coding (HGVS c.)
- NM_177438.2:c.3334A>G
- Protein (HGVS p.)
- NP_803187.1:p.(Asn1112Asp)
- GRCh38
- chr14:95104062 T>C
- GRCh37
- chr14:95570399 T>C
- ClinVar
- 133969
- COSMIC
- COSV58626859
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
—
Transcript span
—
Strand
—
Variants mapped
—
Source
UCSC ncbiRefSeqCurated
All variants in DICER1
—
Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
90 / 1,614,090 alleles
AF 5.58e-05 · 0 homozygotes · FAF 0.00165
gnomAD v2.1
18 / 250,782 alleles
AF 7.18e-05 · 0 homozygotes · FAF 0.000632
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 5.6e-05 · 90 / 1,614,090 alleles · 0 hom · FAF 0.0017
| East Asian89 / 44,880 | 0.002 |
| Remaining individuals1 / 62,506 | 1.6e-05 |
0 alternate alleles recorded in 8 other groups: Admixed American, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish).
gnomAD v2.1
AF 7.2e-05 · 18 / 250,782 alleles · 0 hom · FAF 0.00063
| East Asian18 / 18,382 | 0.00098 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 5.5759e-05; MAF= 0.00558%, 90/1614090 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.00198307; MAF= 0.19831%, 89/44880 alleles, homozygotes = 0); grpmax FAF= 0.00165003.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.17755e-05; MAF= 0.00718%, 18/250782 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000979219; MAF= 0.09792%, 18/18382 alleles, homozygotes = 0); grpmax FAF= 0.0006324.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.109
- BayesDel
- -0.562
How the predictions were used
BP4 SupportingREVEL score of 0.109 is well below the DICER1 VCEP BP4 threshold of <0.500, and SpliceAI predicts no splicing impact (max delta score 0.09). The agreement of multiple in silico predictors supports a benign interpretation. Details ▾Hide ▴
Evidence considered
- REVEL 0.109 (<0.500 BP4 threshold)
- SpliceAI max delta 0.09 (no splicing effect)
- BayesDel -0.562 (benign).
Sources
PP3 REVEL score of 0.109 is well below the DICER1 VCEP PP3 threshold of >=0.750. SpliceAI predicts no splicing impact (max delta 0.09). BayesDel score of -0.562 corroborates a benign prediction. Multiple computational lines of evidence suggest no deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL 0.109 (<0.750 threshold)
- SpliceAI max delta 0.09 (no splicing effect)
- BayesDel -0.562 (benign prediction).
Sources
BP7 N/ABP7 applies only to silent (synonymous) variants, deep intronic variants (at or beyond +7/-21 positions), or non-coding variants where the reference nucleotide is conserved across >=1 primate and/or >=4 mammalian species. NM_177438.2:c.3334A>G is a missense variant (p.Asn1112Asp) and does not meet any BP7 eligibility criteria. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is for silent/intronic/non-coding variants only.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.09). REVEL score = 0.109. BayesDel score = -0.562068.
8 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
-
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 interpretation of sequence variants. General framework document; does not discuss NM_177438.2:c.3334A>G or any specific DICER1 variant.Does not name this variant
-
PMID 26241669 ↗A Novel WRN Frameshift Mutation Identified by Multiplex Genetic Testing in a Family with Multiple Cases of Cancer.Yang L et al. · 2015Reports a novel WRN frameshift mutation identified by multiplex genetic testing in a Chinese family with multiple cancers. DICER1 NM_177438.2:c.3334A>G (p.Asn1112Asp) was not mentioned in this paper.Does not name this variant
-
PMID 29762508 ↗DICER1 Syndrome: DICER1 Mutations in Rare Cancers.Robertson JC et al. · 2018Review article on DICER1 syndrome covering DICER1 mutations in rare cancers. Discusses DICER1 gene function, miRNA biogenesis, and known pathogenic hotspot mutations (RNase IIIb domain), but does not mention p.Asn1112Asp or c.3334A>G.Does not name this variant
-
PMID 24728327 ↗Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.Bodian DL et al. · 2014Characterized germline variation in 158 cancer-susceptibility genes in a healthy, ancestrally diverse cohort of 681 individuals. The full text does not contain the terms DICER1, c.3334A>G, or N1112D in the available portion; however, this variant was catalogued in the study's supplementary data as a rare variant in cancer genes found in healthy individuals, forming the basis for the ITMI ClinVar submission (SCV000084799).Does not name this variant
-
PMID 24761742 ↗DICER1-Related Tumor Predisposition.Adam MP et al. · 1993GeneReviews entry on DICER1-related tumor predisposition. Provides comprehensive clinical and molecular overview of DICER1 syndrome. NM_177438.2:c.3334A>G (p.Asn1112Asp) is not discussed in this resource.Does not name this variant
-
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 referral indications for cancer predisposition assessment. General clinical guideline; does not mention any specific DICER1 variants.Does not name this variant
-
PMID 30093976 ↗Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers.Chan GHJ et al. · 2018Clinical genetic testing outcomes with multi-gene panels in Asian patients with multiple primary cancers (n=231 multi-primary, n=960 single-primary). The available full text does not mention DICER1 p.Asn1112Asp or c.3334A>G. Focus is on BRCA1/2, Lynch syndrome genes, and other high-penetrance cancer genes in an Asian cohort.Does not name this variant
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Nykamp K et al. · 2017Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Provides a systematic framework for variant classification but does not discuss any 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
90 / 1,614,090 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.090
Open source ↗
ClinVar
3 Likely benign · 1 Uncertain significance
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/133969/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/14-95570399-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr14-95104062-T-C?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/14-95104062-T-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_177438.2%3Ac.3334…
- OncoKB ↗www.oncokb.org/gene/DICER1/N1112D
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=188090334
- 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= 5.5759e-05; MAF= 0.00558%, 90/1614090 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.00198307; MAF= 0.19831%, 89/44880 alleles, homozygotes = 0); grpmax FAF= 0.00165003.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.17755e-05; MAF= 0.00718%, 18/250782 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000979219; MAF= 0.09792%, 18/18382 alleles, homozygotes = 0); grpmax FAF= 0.0006324.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Likely benign (3 clinical laboratories) and as Uncertain significance (1 clinical laboratory). (ClinVarID = 133969)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.09). REVEL score = 0.109. BayesDel score = -0.562068.
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 previously been reported in somatic cancers (COSMIC; COSV58626859, n = 3 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.