About DNMT3A
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
DNMT3A c.1055G>A, p.(Ser352Asn)
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 Not recorded. 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: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
The variant is extremely rare in population databases: gnomAD v2.1 AF 0.00425% (12/282,532 alleles, 0 homozygotes, grpmax FAF 6.39e-05) and gnomAD v4.1 AF 0.00675% (109/1,614,124 alleles, 0 homozygotes, grpmax FAF 6.81e-05), both well below the 0.1% PM2 threshold.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple computational predictors support no impact on protein function or splicing: REVEL 0.098 (well below 0.5), BayesDel -0.5207 (negative, benign-leaning), and SpliceAI max delta 0.29 (below the 0.5 high-confidence splice-altering threshold).
Recorded classification: Uncertain significance
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP4 supporting; combination = 1 supporting + 1 supporting benign, 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
109 / 1,614,124 alleles
gnomAD v4.1: 109 / 1,614,124 alleles. Recorded AF 6.75289e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.24731e-05; MAF= 0.00425%, 12/282532 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000163377; MAF= 0.01634%, 5/30604 alleles, homozygotes = 0); grpmax FAF= 6.394e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI score
0.290 maximum delta
Recorded SpliceAI maximum delta score: 0.290. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
2 reported laboratory submissions
2 Uncertain significance. ClinVar API review status: criteria provided, single submitter.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Neutral; curated oncogenicity label: Likely Neutral.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV53049161, 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 Not recorded, with the data and sources behind each one.
29 criteria with recorded statuses: 2 met · 22 not met · 0 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
PVS1 does not apply because p.Ser352Asn is a missense substitution rather than a null variant (nonsense, frameshift, or canonical splice site).
The variant is extremely rare in population databases (gnomAD v2.1 AF 0.00425% and v4.1 AF 0.00675%, no homozygotes), supporting PM2 at supporting strength.
Computational predictors are concordant for a benign effect (REVEL 0.098, BayesDel -0.52, SpliceAI max delta 0.29 below the high-confidence splice threshold), supporting BP4; PP3 is not met.
The variant has been observed as a somatic DNMT3A mutation in a therapy-related/secondary AML patient (PMID:21993668) and is curated as Likely Neutral by OncoKB; the somatic observation does not meet germline PS4, and no variant-specific functional data are available (PS3 not met; BS3 not met because no well-established functional studies exist).
ClinVar classifies the variant as Uncertain significance from two laboratories (1-star, single submitter), so PS5, PP5, and BP6 are not met.
No de novo, segregation, case-control, or phenotype-specific evidence is available, and no same-codon pathogenic comparator was identified, so PS2, PM6, PM5, PP1, and PP4 are not met.
Population allele frequencies are far below the BA1 (1%) and BS1 (0.3%) thresholds, so BA1 and BS1 are not met.
With only PM2 (supporting) and BP4 (supporting) met, no pathogenic or benign combination is reached under the generic ACMG/AMP 2015 rules, consistent with a classification of Uncertain Significance.
No criteria match.
Met · 2
PM2 SupportingThe variant is extremely rare in population databases: gnomAD v2.1 AF 0.00425% (12/282,532 alleles, 0 homozygotes, grpmax FAF 6.39e-05) and gnomAD v4.1 AF 0.00675% (109/1,614,124 alleles, 0 homozygotes, grpmax FAF 6.81e-05), both well below the 0.1% PM2 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF 0.00425%
- 12/282
- 532 alleles
- 0 homozygotes
- grpmax FAF 6.39e-05.
- gnomAD v4.1: AF 0.00675%
- 109/1
- 614
- 124 alleles
- grpmax FAF 6.81e-05.
Sources
BP4 SupportingMultiple computational predictors support no impact on protein function or splicing: REVEL 0.098 (well below 0.5), BayesDel -0.5207 (negative, benign-leaning), and SpliceAI max delta 0.29 (below the 0.5 high-confidence splice-altering threshold). Details ▾Hide ▴
Evidence considered
- REVEL 0.098 - predicted benign.
- BayesDel -0.5207 - predicted benign.
- SpliceAI max delta 0.29 (DS_AL 0.29
- DS_AG 0.28) - below 0.5 high-confidence threshold.
Still missing
- SpliceAI delta 0.29 falls in the possible-splicing range
- no RNA-based confirmation.
Sources
Not met · 22 · evaluated, threshold not reached
PS1 No pathogenic or likely pathogenic variant producing the same amino acid change (p.Ser352Asn) via a different nucleotide substitution was identified in ClinVar or the reviewed literature. Details ▾Hide ▴
Evidence considered
- ClinVar record 2052526 corresponds only to c.1055G>A (p.Ser352Asn)
- no alternate-nucleotide same-amino-acid pathogenic comparator identified.
Still missing
- No systematic search for same-amino-acid variants outside ClinVar.
Sources
PS2 No de novo occurrence of p.Ser352Asn with confirmed or assumed parentage was reported in the available evidence. Details ▾Hide ▴
Evidence considered
- No de novo observation for this variant.
Still missing
- No parental testing or de novo report available.
PS3 No variant-specific functional data exist for p.Ser352Asn. The variant is listed among novel somatic DNMT3A mutations in a t-AML/sAML cohort (PMID:21993668) without functional characterization; the systematic DNMT3A variant profiling study (PMID:34429321) does not include this variant in its available text; and OncoKB's Likely Neutral annotation is a curated label, not experimental evidence. Details ▾Hide ▴
Evidence considered
- PMID:21993668 reports S352N as a somatic DNMT3A mutation in therapy-related/secondary AML
- confirmed somatic via constitutional DNA
- but provides no functional assay.
- PMID:34429321 profiled 253 DNMT3A variants for methyltransferase activity and stability
- S352N is not present in the available full text (tested-variant list is Supplementary Table S1
- not in case materials).
- OncoKB curates S352N as Likely Neutral in the somatic context
- not primary functional evidence.
Still missing
- No direct functional assay (methyltransferase activity or protein stability) for p.Ser352Asn.
Sources
PS4 No evidence of increased variant prevalence in affected individuals versus controls for germline disease. The variant has been observed once as a somatic mutation in therapy-related/secondary AML (PMID:21993668; COSMIC n=1), which does not constitute germline case evidence, and ClinVar reports the variant as Uncertain significance from two laboratories. Details ▾Hide ▴
Evidence considered
- Somatic observation in a single t-AML/sAML patient (PMID:21993668)
- COSMIC COSV53049161
- n=1.
- ClinVar: VUS (2 clinical laboratories)
- no case-control enrichment data.
Still missing
- No germline case-control or cohort prevalence data for this variant.
Sources
PM1 Residue Ser352 lies within the ADD (ATRX-DNMT3A-DNMT3L) domain of DNMT3A (approximately residues 280-430), a well-characterized functional domain; however, p.Ser352Asn is not a statistically significant mutational hotspot, OncoKB curates the substitution as Likely Neutral, and no variant-specific evidence demonstrates disruption of ADD-domain function, so domain-level PM1 is not met. Details ▾Hide ▴
Evidence considered
- Ser352 is located in the ADD domain (H3K4me0 reader / autoinhibitory module of DNMT3A).
- Not a statistically significant hotspot per cancerhotspots.org.
- OncoKB: Likely Neutral (curated somatic oncogenicity label).
Still missing
- No variant-specific functional data on ADD-domain histone binding or DNMT3A activity for p.Ser352Asn.
Sources
PM5 No pathogenic or likely pathogenic missense variant at the same codon (Ser352) with a different amino acid substitution was identified; the automated PM5 candidate search returned no comparators, and the S352D change observed in one somatic AML case (PMID:21993668) is not a germline pathogenic classification. Details ▾Hide ▴
Evidence considered
- PM5 candidate harvest: 0 same-residue pathogenic candidates.
- S352D observed somatically in t-AML (PMID:21993668) - not a germline pathogenic comparator.
Still missing
- No ClinVar P/LP record at codon 352.
Sources
pm5_candidatesPMID:21993668 ↗
PM6 No de novo observation, with or without confirmed parentage, was reported for p.Ser352Asn. Details ▾Hide ▴
Evidence considered
- No de novo evidence available.
Still missing
- No parental testing data.
PP1 No cosegregation data in multiple affected family members are available for p.Ser352Asn. Details ▾Hide ▴
Evidence considered
- No segregation data available.
Still missing
- No family studies available.
PP2 Missense variants are a known mechanism of DNMT3A-related Tatton-Brown-Rahman syndrome, but no gene-specific missense constraint metric (e.g., gnomAD missense Z-score) or VCEP-defined PP2 threshold is available in the case materials to formally apply PP2. Details ▾Hide ▴
Evidence considered
- DNMT3A germline disease mechanism includes missense variants (TBRS
- pvs1_gene_context).
- No formal missense constraint metric or VCEP guidance available.
Still missing
- No gnomAD missense Z-score or VCEP PP2 threshold for DNMT3A.
Sources
pvs1_gene_context
PP3 In silico predictors are concordant for a benign effect - REVEL 0.098 (well below 0.5), BayesDel -0.5207 (negative, benign-leaning), and SpliceAI max delta 0.29 (below the 0.5 high-confidence splice-altering threshold, variant deep in exon 9) - so no computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL 0.098 - predicted benign.
- BayesDel -0.5207 - predicted benign.
- SpliceAI max delta 0.29 (DS_AL 0.29
- DS_AG 0.28) - below 0.5 high-confidence threshold.
Still missing
- SpliceAI delta 0.29 is in the possible-splicing range (0.2-0.5)
- no RNA-based confirmation.
Sources
PP4 No proband phenotype data are available to establish a phenotype highly specific for DNMT3A-related disease. Details ▾Hide ▴
Evidence considered
- No patient phenotype data available.
Still missing
- No clinical phenotype provided for the proband.
PP5 ClinVar classifies p.Ser352Asn as Uncertain significance (2 laboratories; criteria provided, single submitter - 1 star), which does not meet the 3-star expert-panel threshold required for PP5, and the TBRS GeneReviews article (PMID:35771960) provides no variant-specific information in the available materials. Details ▾Hide ▴
Evidence considered
- ClinVar VUS
- 1-star single-submitter
- not an expert-panel pathogenic classification.
- PMID:35771960 (TBRS GeneReviews): no abstract or full text in the packet
- cannot be confirmed to mention this variant.
Still missing
- Full text of PMID:35771960 not available for variant-level confirmation.
Sources
BA1 The maximum allele frequency is 0.00675% (gnomAD v4.1), far below the 1% BA1 threshold. Details ▾Hide ▴
BS1 The highest subpopulation allele frequency is 0.01634% (South Asian, gnomAD v2.1), far below the 0.3% BS1 threshold. Details ▾Hide ▴
Evidence considered
- Highest subpopulation AF 0.01634% (South Asian
- gnomAD v2.1) - well below the 0.3% BS1 threshold.
Sources
BS2 The variant is present at very low frequency in gnomAD with no homozygotes, and no age- or phenotype-stratified healthy-adult cohort data demonstrate observation at a frequency consistent with a fully penetrant benign allele. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 12 alleles
- 0 homozygotes
- gnomAD v4.1: 109 alleles
- 0 homozygotes.
- No healthy-adult/age-stratified control data.
Still missing
- No age-stratified healthy control cohort data.
Sources
BS3 No well-established functional studies demonstrate a lack of damaging effect for p.Ser352Asn. OncoKB's Likely Neutral annotation is a curated somatic oncogenicity label rather than experimental evidence, and in silico scores (REVEL 0.098, BayesDel -0.52) are predictive rather than functional. Details ▾Hide ▴
Evidence considered
- OncoKB Likely Neutral - curated literature annotation
- not an experimental assay.
- REVEL and BayesDel are computational predictors
- not functional studies.
Still missing
- No in vitro or in vivo assay of DNMT3A function for this variant.
Sources
BS4 No segregation data demonstrating absence of cosegregation with disease in affected families are available. Details ▾Hide ▴
Evidence considered
- No segregation data available.
Still missing
- No family studies available.
BP1 DNMT3A-related disease (Tatton-Brown-Rahman syndrome) is caused by both truncating and missense variants, so missense is a known disease mechanism and BP1 does not apply. Details ▾Hide ▴
Evidence considered
- DNMT3A germline disease is associated with both truncating and missense variants
- missense is a known mechanism.
Sources
pvs1_gene_context
BP2 No observation of the variant in trans with a known pathogenic DNMT3A variant in an affected individual is available. Details ▾Hide ▴
Evidence considered
- No trans-phase observation data available.
Still missing
- No phase data with pathogenic DNMT3A variants.
BP5 No alternate molecular basis of disease has been documented in a carrier of this variant. Details ▾Hide ▴
Evidence considered
- No alternate-diagnosis data for variant carriers.
Still missing
- No alternate molecular basis data available.
BP6 ClinVar does not classify p.Ser352Asn as benign or likely benign by an expert panel (VUS, 1-star single submitter), so BP6 does not apply. Details ▾Hide ▴
Evidence considered
- ClinVar: VUS
- criteria provided single submitter
- not a 3-star expert-panel benign classification.
Sources
PS5 No reputable source classifies p.Ser352Asn as pathogenic; ClinVar lists the variant as Uncertain significance with criteria provided by a single submitter. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Uncertain significance (2 laboratories
- 1-star
- criteria provided
- single submitter).
Sources
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_022552.4:c.1055G>A is a missense substitution (p.Ser352Asn, exon 9) and does not fall into the null-variant buckets (nonsense, frameshift, canonical +-1/2 splice) required for PVS1 under the ClinGen SVI PVS1 framework. Details ▾Hide ▴
Evidence considered
- Missense substitution
- not a null variant.
- Variant-level PVS1 scaffold: apply_generic_pvs1_framework=false
- not nonsense/frameshift/canonical splice.
Sources
pvs1_generic_framework ↗pvs1_variant_assessment
PM3 N/APM3 requires trans-phase observation with a pathogenic variant, which is not applicable for this autosomal-dominant context with no such data; skipped. Details ▾Hide ▴
Evidence considered
- No trans-phase data
- PM3 skipped.
PM4 N/APM4 applies to protein-length-changing variants (in-frame indel or stop-loss); this is a substitution variant. Details ▾Hide ▴
Evidence considered
- Substitution variant
- PM4 skipped.
BP3 N/ABP3 applies only to in-frame insertions/deletions in repetitive regions; this is a substitution variant. Details ▾Hide ▴
Evidence considered
- Substitution variant
- BP3 skipped.
BP7 N/ABP7 applies to synonymous variants without predicted splice impact; c.1055G>A is a missense substitution (p.Ser352Asn). Details ▾Hide ▴
Evidence considered
- Missense variant
- not synonymous.
Identifiers
- Gene
- DNMT3A
- Transcript
- NM_022552.4
- Coding (HGVS c.)
- NM_022552.4:c.1055G>A
- Protein (HGVS p.)
- NP_072046.2:p.(Ser352Asn)
- GRCh38
- chr2:25247118 C>T
- GRCh37
- chr2:25469987 C>T
- ClinVar
- 2052526
- COSMIC
- COSV53049161
Gene diagram
Every interpreted variant in DNMT3A, mapped onto the exon structure of NM_022552.4. Select a row to find it on the plot.
DNMT3ANM_022552.4
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 DNMT3A
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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
109 / 1,614,124 alleles
AF 6.75e-05 · 0 homozygotes · FAF 6.81e-05
gnomAD v2.1
12 / 282,532 alleles
AF 4.25e-05 · 0 homozygotes · FAF 6.39e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 6.8e-05 · 109 / 1,614,124 alleles · 0 hom · FAF 6.8e-05
| European (non-Finnish)96 / 1,179,994 | 8.1e-05 |
| South Asian7 / 91,082 | 7.7e-05 |
| Remaining individuals3 / 62,510 | 4.8e-05 |
| African/African American3 / 75,022 | 4e-05 |
0 alternate alleles recorded in 6 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 4.2e-05 · 12 / 282,532 alleles · 0 hom · FAF 6.4e-05
| South Asian5 / 30,604 | 0.00016 |
| European (non-Finnish)7 / 128,948 | 5.4e-05 |
0 alternate alleles recorded in 6 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 6.75289e-05; MAF= 0.00675%, 109/1614124 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.13563e-05; MAF= 0.00814%, 96/1179994 alleles, homozygotes = 0); grpmax FAF= 6.807e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.24731e-05; MAF= 0.00425%, 12/282532 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000163377; MAF= 0.01634%, 5/30604 alleles, homozygotes = 0); grpmax FAF= 6.394e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.098
- BayesDel
- -0.521
How the predictions were used
BP4 SupportingMultiple computational predictors support no impact on protein function or splicing: REVEL 0.098 (well below 0.5), BayesDel -0.5207 (negative, benign-leaning), and SpliceAI max delta 0.29 (below the 0.5 high-confidence splice-altering threshold). Details ▾Hide ▴
Evidence considered
- REVEL 0.098 - predicted benign.
- BayesDel -0.5207 - predicted benign.
- SpliceAI max delta 0.29 (DS_AL 0.29
- DS_AG 0.28) - below 0.5 high-confidence threshold.
Still missing
- SpliceAI delta 0.29 falls in the possible-splicing range
- no RNA-based confirmation.
Sources
PP3 In silico predictors are concordant for a benign effect - REVEL 0.098 (well below 0.5), BayesDel -0.5207 (negative, benign-leaning), and SpliceAI max delta 0.29 (below the 0.5 high-confidence splice-altering threshold, variant deep in exon 9) - so no computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL 0.098 - predicted benign.
- BayesDel -0.5207 - predicted benign.
- SpliceAI max delta 0.29 (DS_AL 0.29
- DS_AG 0.28) - below 0.5 high-confidence threshold.
Still missing
- SpliceAI delta 0.29 is in the possible-splicing range (0.2-0.5)
- no RNA-based confirmation.
Sources
BP7 N/ABP7 applies to synonymous variants without predicted splice impact; c.1055G>A is a missense substitution (p.Ser352Asn). Details ▾Hide ▴
Evidence considered
- Missense variant
- not synonymous.
Statement
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.29). REVEL score = 0.098. BayesDel score = -0.520724.
3 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Recorded publications
-
PMID 21993668 ↗Frequency, onset and clinical impact of somatic DNMT3A mutations in therapy-related and secondary acute myeloid leukemia.Reports DNMT3A S352N as one of the novel somatic mutations identified in a cohort of 98 patients with therapy-related or secondary acute myeloid leukemia. The somatic origin of S352N and other listed mutations was confirmed by testing constitutional DNA; a second variant at the same codon, S352D, is listed in Table 1 for a separate t-AML patient.Names this variant
Quoted passage
Since most of our identified mutations (S352N, W581C, V636M, I655A, F731C, Y735C, F752L, W753G, L754R, W795C, P849R, L889P, A910V) have not been reported previously, we tested constitutional DNA to prove the somatic nature of these mutations
Results, paragraph describing the DNMT3A mutation spectrum (following Table 1); Table 1 (S352D case).
-
PMID 34429321 ↗Systematic Profiling of DNMT3A Variants Reveals Protein Instability Mediated by the DCAF8 E3 Ubiquitin Ligase Adaptor.Systematically profiled 253 disease-associated DNMT3A missense variants for methyltransferase activity (HOXA5-Snrpn-BFP reporter) and protein stability, finding that 74% cause severe loss of function and 37% reduce protein stability, with instability mediated by the DCAF8/CUL4B ubiquitin ligase. p.Ser352Asn is not present in the available full text; the tested-variant list is in Supplementary Table S1, which is not part of the case materials.Does not name this variant
-
PMID 35771960 ↗Tatton-Brown-Rahman Syndrome.Adam MP et al. · 1993GeneReviews overview of Tatton-Brown-Rahman syndrome (germline DNMT3A-related overgrowth disorder) providing gene-level clinical context; no variant-specific data are available in the case materials (no abstract or full text retrieved).Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
109 / 1,614,124 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.290
Open source ↗
ClinVar
2 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 ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/2052526/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-25469987-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-25247118-C-T?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-25247118-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_022552.4%3Ac.1055…
- OncoKB ↗www.oncokb.org/gene/DNMT3A/S352N
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=122050354
- 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= 6.75289e-05; MAF= 0.00675%, 109/1614124 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.13563e-05; MAF= 0.00814%, 96/1179994 alleles, homozygotes = 0); grpmax FAF= 6.807e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.24731e-05; MAF= 0.00425%, 12/282532 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000163377; MAF= 0.01634%, 5/30604 alleles, homozygotes = 0); grpmax FAF= 6.394e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (2 clinical laboratories). (ClinVarID = 2052526)
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.29). REVEL score = 0.098. BayesDel score = -0.520724.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Neutral; curated oncogenicity label: Likely Neutral.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV53049161, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.