About DICER1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
DICER1 c.1468C>T, p.(Arg490Cys)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
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: 0
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
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: no point-contributing criteria = 0 points, which maps to VUS.
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
44 / 1,613,964 alleles
gnomAD v4.1: 44 / 1,613,964 alleles. Recorded AF 2.72621e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18318e-05; MAF= 0.00318%, 9/282736 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 9.80008e-05; MAF= 0.00980%, 3/30612 alleles, homozygotes = 0); grpmax FAF= 2.596e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
No listed criterion applied
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
6 reported laboratory submissions
5 Uncertain significance · 1 Likely benign. 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
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV58627328, n = 1 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 v1.4.0, with the data and sources behind each one.
29 criteria with recorded statuses: 0 met · 17 not met · 0 not assessed · 12 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.1468C>T (p.Arg490Cys) is a missense variant in exon 9 of DICER1.
This variant is present in gnomAD v4.1 at an overall allele frequency of 2.73e-05 (44/1,613,964 alleles) and at 3.18e-05 in v2.1 (9/282,736 alleles), with the highest subpopulation frequency in South Asians (v4.1: 0.00011). No homozygotes have been observed.
The variant does not meet the VCEP PM2 threshold (AF < 5.0e-06 with ≤1 allele per subpopulation), as the overall frequency exceeds this cutoff and multiple alleles are present in the South Asian subpopulation.
The variant has been reported in ClinVar (Variation ID 242039) as Uncertain significance by multiple clinical laboratories and as Likely benign by one submitter; review status is 'criteria provided, single submitter' with no expert panel classification.
The variant was observed as a somatic finding in one pineoblastoma tumor (RBTC779, MYC subgroup) without evident loss of heterozygosity, described as 'potentially deleterious' in a study of pineoblastoma molecular subgroups.
Computational predictors are indeterminate: REVEL score is 0.502 (borderline; VCEP PP3 requires ≥0.750, BP4 requires <0.500), SpliceAI predicts no splicing impact (max delta = 0.00), and BayesDel score is 0.158.
The variant is located at p.Arg490, which lies outside the VCEP-defined metal ion-binding residues and RNase IIIb domain; it is not in a statistically significant cancer hotspot.
No functional studies, de novo observations, segregation data, or tumor second-hit data were identified that would support application of any pathogenic or benign criterion at any strength level under the ClinGen DICER1 VCEP v1.4.0 framework.
Under the VCEP Tavtigian point-based system, no criteria are met in either the pathogenic or benign direction, yielding a total point value of 0, which classifies as Uncertain Significance (Rule3: -1 to 5 points).
No criteria match.
Not met · 17 · evaluated, threshold not reached
PS1 PS1 requires a different nucleotide change at the same amino acid position previously classified as pathogenic by the ClinGen DICER1 VCEP. No such comparator variant was identified. Details ▾Hide ▴
Evidence considered
- VCEP PS1 requires a same-amino-acid pathogenic comparator classified by the DICER1 VCEP. No candidate comparator was found.
Still missing
- No VCEP-classified pathogenic variant at p.Arg490 available for comparison.
Sources
PS2 No de novo observations were identified in the literature or ClinVar submissions for this variant. VCEP PS2 requires documented de novo events with confirmed parentage. Details ▾Hide ▴
Evidence considered
- No de novo data available for NM_177438.2:c.1468C>T.
Still missing
- No de novo reports identified in ClinVar or literature.
PS3 No functional studies (RNA assay, in vitro cleavage assay, or other validated functional data) were identified for this variant. SpliceAI predicts no splicing impact (max delta = 0.00). OncoKB reports no variant-specific functional evidence. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score = 0.00
- no splicing impact. OncoKB reports Unknown Oncogenic Effect with no variant-specific functional data. No RNA or cleavage assay data available.
Still missing
- No functional studies performed on p.Arg490Cys.
Sources
PS4 No variant-specific proband counts or phenotype points meeting VCEP PS4 thresholds were identified. The variant was observed as a somatic finding in one pineoblastoma tumor (PMID:31820118) but this does not constitute independent germline proband evidence. Details ▾Hide ▴
Evidence considered
- Variant observed in one pineoblastoma tumor (RBTC779
- MYC subgroup) without evident LOH
- described as 'potentially deleterious' — somatic context
- insufficient for germline PS4 phenotype points.
Still missing
- No unrelated germline probands with DICER1-associated phenotypes identified.
Sources
PM1 The variant is at p.Arg490, which lies outside the VCEP-defined metal ion-binding residues (p.S1344, p.E1705, p.D1709, p.D1713, p.G1809, p.D1810, p.E1813) and outside the RNase IIIb domain (p.Y1682–p.S1846). The residue is not in a statistically significant cancer hotspot. Details ▾Hide ▴
Evidence considered
- VCEP PM1 Moderate applies only to metal ion-binding residues
- PM1 Supporting applies only within RNase IIIb domain (p.Y1682–p.S1846). p.R490 is in the helicase domain region
- far from both.
Sources
PM2 gnomAD v4.1 overall AF = 2.73e-05 exceeds the VCEP PM2 threshold of <5.0e-06. Additionally, 10 alleles are present in the South Asian subpopulation (AF = 0.00011), violating the 'no more than one allele in any subpopulation' requirement. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 44/1
- 613
- 964 alleles (AF=2.73e-05)
- grpmax FAF=5.94e-05. SAS: 10/91
- 078 (AF=0.00011). gnomAD v2.1: 9/282
- 736 (AF=3.18e-05). VCEP PM2 requires AF < 0.000005 and ≤1 allele per subpopulation — both conditions fail.
Sources
PM5 No pathogenic missense comparator at the same residue (p.Arg490) classified by the ClinGen DICER1 VCEP was identified. PM5 candidate search returned zero same-residue candidates. Details ▾Hide ▴
Evidence considered
- VCEP PM5 requires a different missense change at the same codon previously classified as pathogenic by the DICER1 VCEP. No candidates found.
Still missing
- No VCEP-classified pathogenic comparator at p.Arg490.
Sources
PP1 No co-segregation data across affected family members were identified. VCEP PP1 requires at least 3–4 meioses for supporting-level evidence. Details ▾Hide ▴
Evidence considered
- No segregation data available for this variant.
Still missing
- No family segregation studies identified.
PP3 REVEL score = 0.502, which is below the VCEP PP3 threshold of ≥0.750. SpliceAI predicts no splicing impact (max delta = 0.00). Neither computational criterion for pathogenicity is satisfied. Details ▾Hide ▴
Evidence considered
- REVEL = 0.502 (< 0.750 threshold). SpliceAI max delta = 0.00 (no splicing effect predicted). VCEP PP3 requires REVEL ≥ 0.750 OR splicing predictor agreement for deleterious splicing.
Sources
PP4 VCEP PP4 requires somatic tumor testing demonstrating a known RNase IIIb hotspot second hit in a DICER1-associated neoplasm, with retention of the germline variant. No such tumor testing data were provided for this case. Details ▾Hide ▴
Evidence considered
- No somatic tumor testing demonstrating a canonical RNase IIIb hotspot second hit with germline variant retention was available.
Still missing
- No tumor sequencing data showing classic DICER1 second-hit pattern.
Sources
BA1 Highest gnomAD subpopulation AF is 0.00011 (South Asian, v4.1), far below the VCEP BA1 threshold of >0.003 (0.3%). Details ▾Hide ▴
Evidence considered
- SAS v4.1 AF = 0.00011 (10/91
- 078)
- SAS v2.1 AF = 0.000098 (3/30
- 612). Both well below BA1 threshold of >0.003.
Sources
BS1 Highest gnomAD subpopulation AF is 0.00011 (South Asian, v4.1), below the VCEP BS1 threshold of >0.0003 (0.03%) and with fewer than the minimum 5 alleles required in the v2.1 SAS subpopulation (3 alleles). Details ▾Hide ▴
Evidence considered
- SAS v4.1: AF=0.00011
- 10 alleles in 91
- 078 — AF < 0.0003. SAS v2.1: AF=0.000098
- 3 alleles in 30
- 612 — fails the 'minimum 5 alleles' requirement. BS1 not met.
Sources
BS2 No data on tumor-free females through age 50 or homozygous observations in healthy individuals were available for this variant. Details ▾Hide ▴
Evidence considered
- No BS2-qualifying observations (tumor-free females
- homozygosity in healthy individuals) identified.
Still missing
- No population-level phenotype data available.
BS3 No in vitro or in vivo functional studies demonstrating no damaging effect on DICER1 protein function or splicing were identified for this variant. Details ▾Hide ▴
Evidence considered
- No functional studies showing benign effect for p.Arg490Cys available.
Still missing
- No functional characterization of this variant.
BS4 No segregation data demonstrating phenotype-positive, genotype-negative relatives were identified. VCEP BS4 requires affected relatives who are genotype-negative. Details ▾Hide ▴
Evidence considered
- No segregation data available.
Still missing
- No family studies available.
BP2 No observations of this variant in trans with a P/LP DICER1 variant or in cis/phase unknown with multiple P/LP DICER1 variants were identified. Details ▾Hide ▴
Evidence considered
- No phase data available.
Still missing
- No in trans or cis observations with other DICER1 variants.
BP4 REVEL score = 0.502, which is not < 0.500 as required by VCEP BP4 for missense variants. Although SpliceAI predicts no splicing impact, the REVEL score does not satisfy the BP4 threshold. Details ▾Hide ▴
Evidence considered
- REVEL = 0.502 (not < 0.500). SpliceAI max delta = 0.00. VCEP BP4 requires REVEL < 0.500 AND no splicing effects — REVEL criterion not satisfied.
Sources
Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis is a missense substitution (p.Arg490Cys). VCEP PVS1 rules apply only to nonsense, frameshift, and canonical splice site variants. The variant does not fall into any PVS1 null-variant bucket. Details ▾Hide ▴
Evidence considered
- VCEP DICER1 v1.4.0 restricts PVS1 to nonsense
- frameshift
- and canonical ±1
- 2 splice variants. This is a missense variant not eligible for PVS1.
Sources
PM3 VCEPDICER1-related tumor predisposition is autosomal dominant. PM3 (in trans with pathogenic variant) is not applicable. Details ▾Hide ▴
PM4 N/APM4 applies to in-frame indels and stop-loss variants. This is a missense substitution. Details ▾Hide ▴
Evidence considered
- Not applicable to missense variants.
PM6 VCEPVCEP combines PM6 with PS2 and directs use of PS2 exclusively for de novo evidence. Per VCEP v1.4.0, PM6 is not applicable. Details ▾Hide ▴
PP2 VCEPVCEP recommends PP2 not be used for DICER1 due to the presence of multiple benign/likely benign missense variants in ClinVar despite a high missense constraint z-score. Details ▾Hide ▴
Evidence considered
- 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 (9) or likely benign (30) in ClinVar.'
Sources
PP5 VCEPVCEP declares PP5 'Not Applicable for this VCEP' per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation. Details ▾Hide ▴
Evidence considered
- VCEP: 'This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.'
Sources
BP1 VCEPVCEP declares BP1 not applicable for DICER1 because truncating variants account for only a portion of disease-causing variants. Details ▾Hide ▴
Evidence considered
- VCEP: 'This rule code does not apply to this gene
- as truncating variants account for only a portion of disease-causing variants.'
Sources
BP3 VCEPBP3 applies to in-frame deletions/insertions in repetitive regions. This is a missense substitution. Details ▾Hide ▴
Evidence considered
- Not applicable to missense variants.
BP5 VCEPVCEP declares BP5 not applicable due to the broad spectrum of DICER1-related neoplasms and lack of evidence for alternative high-penetrance germline variants. Details ▾Hide ▴
Evidence considered
- VCEP: 'Given the broad spectrum of DICER1-related neoplasms ... this rule should not be used at this time.'
Sources
BP6 VCEPVCEP declares BP6 'Not Applicable for this VCEP' per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation. Details ▾Hide ▴
Evidence considered
- VCEP: 'This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.'
Sources
BP7 N/ABP7 applies to silent, intronic, or non-coding variants. This is a missense substitution (p.Arg490Cys) and does not qualify. Additionally, BP7 requires BP4 to be met, which it is not. Details ▾Hide ▴
Evidence considered
- VCEP BP7 applies only to silent/intronic/non-coding variants. This is a missense variant. BP4 prerequisite also not met.
Sources
PS5 N/APS5 is not a standard ACMG/AMP criterion and is not included in the ClinGen DICER1 VCEP v1.4.0 specifications. Details ▾Hide ▴
Evidence considered
- Not part of the VCEP framework.
Identifiers
- Gene
- DICER1
- Transcript
- NM_177438.2
- Coding (HGVS c.)
- NM_177438.2:c.1468C>T
- Protein (HGVS p.)
- NP_803187.1:p.(Arg490Cys)
- GRCh38
- chr14:95117663 G>A
- GRCh37
- chr14:95584000 G>A
- ClinVar
- 242039
- COSMIC
- COSV58627328
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
44 / 1,613,964 alleles
AF 2.73e-05 · 0 homozygotes · FAF 5.94e-05
gnomAD v2.1
9 / 282,736 alleles
AF 3.18e-05 · 0 homozygotes · FAF 2.6e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 2.7e-05 · 44 / 1,613,964 alleles · 0 hom · FAF 5.9e-05
| South Asian10 / 91,078 | 0.00011 |
| Remaining individuals4 / 62,500 | 6.4e-05 |
| Admixed American3 / 59,998 | 5e-05 |
| East Asian2 / 44,874 | 4.5e-05 |
| European (non-Finnish)24 / 1,179,940 | 2e-05 |
| African/African American1 / 75,002 | 1.3e-05 |
0 alternate alleles recorded in 4 other groups: European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 3.2e-05 · 9 / 282,736 alleles · 0 hom · FAF 2.6e-05
| South Asian3 / 30,612 | 9.8e-05 |
| East Asian1 / 19,952 | 5e-05 |
| African/African American1 / 24,964 | 4e-05 |
| Admixed American1 / 35,438 | 2.8e-05 |
| European (non-Finnish)3 / 129,066 | 2.3e-05 |
0 alternate alleles recorded in 3 other groups: Ashkenazi Jewish, European (Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 2.72621e-05; MAF= 0.00273%, 44/1613964 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000109796; MAF= 0.01098%, 10/91078 alleles, homozygotes = 0); grpmax FAF= 5.937e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18318e-05; MAF= 0.00318%, 9/282736 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 9.80008e-05; MAF= 0.00980%, 3/30612 alleles, homozygotes = 0); grpmax FAF= 2.596e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.502
- BayesDel
- 0.158
How the predictions were used
PP3 REVEL score = 0.502, which is below the VCEP PP3 threshold of ≥0.750. SpliceAI predicts no splicing impact (max delta = 0.00). Neither computational criterion for pathogenicity is satisfied. Details ▾Hide ▴
Evidence considered
- REVEL = 0.502 (< 0.750 threshold). SpliceAI max delta = 0.00 (no splicing effect predicted). VCEP PP3 requires REVEL ≥ 0.750 OR splicing predictor agreement for deleterious splicing.
Sources
BP4 REVEL score = 0.502, which is not < 0.500 as required by VCEP BP4 for missense variants. Although SpliceAI predicts no splicing impact, the REVEL score does not satisfy the BP4 threshold. Details ▾Hide ▴
Evidence considered
- REVEL = 0.502 (not < 0.500). SpliceAI max delta = 0.00. VCEP BP4 requires REVEL < 0.500 AND no splicing effects — REVEL criterion not satisfied.
Sources
BP7 N/ABP7 applies to silent, intronic, or non-coding variants. This is a missense substitution (p.Arg490Cys) and does not qualify. Additionally, BP7 requires BP4 to be met, which it is not. Details ▾Hide ▴
Evidence considered
- VCEP BP7 applies only to silent/intronic/non-coding variants. This is a missense variant. BP4 prerequisite also not met.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.502. BayesDel score = 0.158285.
6 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. · 2015This is the ACMG/AMP 2015 standards and guidelines for variant interpretation (Richards et al.). It provides the generic classification framework and does not discuss any specific DICER1 variant.Does not name this variant
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PMID 31820118 ↗Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study.Li BK et al. · 2020DICER1 c.1468N>T (p.R490C) was identified as a somatic, potentially deleterious missense mutation without evident loss of heterozygosity in a single pineoblastoma tumor (RBTC779, MYC molecular subgroup). The variant was not among the 5 germline DICER1 mutations reported in this study.Names this variant
Quoted passage
In contrast to group 1 and 2 tumors, sequencing of 22 RB and MYC sub-group PBs revealed only two potentially deleterious DICER1 mutations without evident LOH, one each in a MYC (RBTC779, c.1468N>T; p.R490C) and a RB subgroup (RBTC758, c.5240C>T; p.S1747L) tumor.
Results section, paragraph describing miRNA biogenesis defects
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PMID 38084291 ↗Specifications of the ACMG/AMP Variant Classification Guidelines for Germline DICER1 Variant Curation.Hatton JN et al. · 2023This publication describes the ClinGen DICER1 VCEP specifications (v1.0) for variant classification. It details the gene-specific criteria rules but does not discuss the specific variant NM_177438.2:c.1468C>T.Does not name this variant
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PMID 24761742 ↗DICER1-Related Tumor Predisposition.Adam MP et al. · 1993This GeneReviews entry covers DICER1-related tumor predisposition at the gene level. The variant NM_177438.2:c.1468C>T was not identified in the available record.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. · 2015This is a practice guideline for cancer genetics referral indications (Hampel et al. 2015). It provides general referral criteria for hereditary cancer syndromes and does not discuss any specific DICER1 variant.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. · 2017This publication describes the Sherloc variant classification framework, a refinement of ACMG-AMP criteria. It 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
44 / 1,613,964 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
5 Uncertain significance · 1 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/242039/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/14-95584000-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr14-95117663-G-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/14-95117663-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_177438.2%3Ac.1468…
- OncoKB ↗www.oncokb.org/gene/DICER1/R490C
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=188088667
- 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= 2.72621e-05; MAF= 0.00273%, 44/1613964 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000109796; MAF= 0.01098%, 10/91078 alleles, homozygotes = 0); grpmax FAF= 5.937e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18318e-05; MAF= 0.00318%, 9/282736 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 9.80008e-05; MAF= 0.00980%, 3/30612 alleles, homozygotes = 0); grpmax FAF= 2.596e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (5 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 242039)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.502. BayesDel score = 0.158285.
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; COSV58627328, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.