About IDH2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
IDH2 c.516G>C, p.(Arg172Ser)
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: 2
Benign evidence criteria: 0
Pathogenic criteria applied · 2
PM1Supporting
PM1 · supporting
p.Arg172 is the critical active site residue of IDH2, analogous to IDH1 R132. This residue is a well-characterized functional domain where somatic missense mutations (R172K, R172M, R172W, R172G, R172S) produce neomorphic enzyme activity converting α-ketoglutarate to the oncometabolite 2-hydroxyglutarate. The residue is in a statistically significant mutational hotspot (cancerhotspots.org), OncoKB classifies R172S as oncogenic, and PMID:24403254 confirmed R172S as a recurrent somatic mutation in osteosarcoma (3/12 patients).
PM2Supporting
PM2 · supporting
NM_002168.3:c.516G>C is absent from gnomAD v2.1 and extremely rare in gnomAD v4.1 (AF = 6.19 × 10⁻⁷; 1/1,614,224 alleles; 0 homozygotes). The highest subpopulation frequency is in Ashkenazi Jewish (AF = 3.38 × 10⁻⁵; 1/29,606 alleles). Allele frequency is far below the PM2 threshold of <0.1% in all populations, consistent with a rare variant.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
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: PM1 supporting, PM2 supporting; combination = 2 supporting, 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
1 / 1,614,224 alleles
gnomAD v4.1: 1 / 1,614,224 alleles. Recorded AF 6.19493e-07. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded. ClinVar API review status: no assertion criteria provided.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; curated oncogenicity label: Oncogenic.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
35 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV57468772, n = 35 times).
Cancer Hotspots
This variant lies 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.
27 criteria with recorded statuses: 2 met · 21 not met · 0 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
PM1 (supporting): p.Arg172 is the critical active site residue of IDH2, a well-characterized functional domain and statistically significant mutational hotspot where somatic missense mutations produce neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate. OncoKB classifies R172S as oncogenic, and PMID:24403254 confirmed R172S as a recurrent somatic mutation in 3/12 osteosarcoma patients.
PM2 (supporting): NM_002168.3:c.516G>C is absent from gnomAD v2.1 and extremely rare in gnomAD v4.1 (AF = 6.19 × 10⁻⁷; 1/1,614,224 alleles; 0 homozygotes), far below the PM2 threshold of <0.1%.
Two supporting criteria for pathogenicity (PM1_supporting + PM2_supporting) are met with no benign criteria met. Per the generic ACMG/AMP 2015 classification combination rules (PMID:25741868), this combination does not reach the threshold for Likely Pathogenic (minimum requires ≥1 moderate and ≥4 supporting, or ≥2 moderate and ≥2 supporting, or ≥1 strong and ≥2 supporting). The variant is classified as a Variant of Uncertain Significance (VUS).
No criteria match.
Met · 2
PM1 Supportingp.Arg172 is the critical active site residue of IDH2, analogous to IDH1 R132. This residue is a well-characterized functional domain where somatic missense mutations (R172K, R172M, R172W, R172G, R172S) produce neomorphic enzyme activity converting α-ketoglutarate to the oncometabolite 2-hydroxyglutarate. The residue is in a statistically significant mutational hotspot (cancerhotspots.org), OncoKB classifies R172S as oncogenic, and PMID:24403254 confirmed R172S as a recurrent somatic mutation in osteosarcoma (3/12 patients). Details ▾Hide ▴
Evidence considered
- Residue R172 is the IDH2 active site
- a critical functional domain.
- Statistically significant hotspot at cancerhotspots.org.
- OncoKB classification: Oncogenic.
- PMID:24403254: R172S identified in 3/12 osteosarcoma patients
- confirming recurrent mutation at this residue.
Sources
PM2 SupportingNM_002168.3:c.516G>C is absent from gnomAD v2.1 and extremely rare in gnomAD v4.1 (AF = 6.19 × 10⁻⁷; 1/1,614,224 alleles; 0 homozygotes). The highest subpopulation frequency is in Ashkenazi Jewish (AF = 3.38 × 10⁻⁵; 1/29,606 alleles). Allele frequency is far below the PM2 threshold of <0.1% in all populations, consistent with a rare variant. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: absent.
- gnomAD v4.1: AF = 6.19e-07 (1/1
- 614
- 224)
- homozygotes = 0.
- Highest subpopulation AF: Ashkenazi Jewish 3.38e-05 (1/29
- 606).
Sources
Not met · 21 · evaluated, threshold not reached
PS1 No evidence that a different nucleotide change at c.516 leading to the same p.Arg172Ser amino acid substitution has been established as pathogenic. The ClinVar record (375985) is for this exact nucleotide change and is classified as risk factor with no assertion criteria provided. Details ▾Hide ▴
Evidence considered
- ClinVar variation 375985 is the same nucleotide change
- not a different nucleotide change producing the same amino acid change.
Still missing
- No alternate nucleotide change producing p.Arg172Ser identified in ClinVar or literature.
Sources
PS2 No de novo data available for this variant. No case reports or family studies documenting confirmed de novo occurrence of NM_002168.3:c.516G>C. Details ▾Hide ▴
Still missing
- No de novo studies or parent-of-origin testing data available.
PS3 No variant-specific functional assay demonstrating a deleterious effect for p.Arg172Ser (R172S) was identified. PMID:20171147 demonstrated neomorphic 2HG-producing activity for IDH2 R172 mutants but specifically tested R172K, not R172S. PMID:24403254 identified R172S in 3/12 osteosarcoma patients and performed antibody-based detection (MsMab-1) but reported no morphological or growth difference between IDH2-WT and IDH2-R172S in transfected U-2 OS cells. No systematic saturation mutagenesis or tiling screen at residue R172 has characterized R172S. Domain-level inference from sparse testing qualifies for PM1, not PS3. Details ▾Hide ▴
Evidence considered
- PMID:20171147 characterized neomorphic activity of IDH2 R172 mutants but specifically tested R172K
- not R172S.
- PMID:24403254 performed antibody validation of R172S with no functional effect on cell growth or migration in U-2 OS cells.
Still missing
- No direct functional assay (enzymatic activity
- 2HG production) specifically testing p.Arg172Ser.
- No saturation mutagenesis or systematic tiling screen covering R172.
Sources
PS4 No case-control data comparing variant prevalence in affected individuals versus controls. The ClinVar submission (SCV002047547) is from a case-control study but is classified as somatic origin with risk factor classification and no assertion criteria provided. This does not satisfy PS4 requirements. Details ▾Hide ▴
Evidence considered
- ClinVar SCV002047547: case-control method
- somatic origin
- risk factor classification
- no criteria provided.
Still missing
- No germline case-control prevalence data available.
Sources
PM5 No same-residue pathogenic comparator with a different amino acid change was identified in ClinVar. While the literature describes R172K, R172M, R172W, and R172G as recurrent IDH2 mutations in gliomas and AML, automated PM5 candidate harvesting found no eligible ClinVar entries with expert panel or majority pathogenic classification at this codon. Without a ClinVar-confirmed pathogenic comparator at the same residue with a different amino acid change, PM5 cannot be applied. Details ▾Hide ▴
Evidence considered
- pm5_candidates.json: total_candidates_seen = 0
- no same-residue ClinVar pathogenic comparators identified.
Still missing
- Other R172 substitutions (R172K
- R172M
- R172W
- R172G) are known from literature but lack structured ClinVar pathogenic classifications for PM5 application.
Sources
pm5_candidates
PM6 No de novo data available. No publications or ClinVar submissions report confirmed de novo occurrence of NM_002168.3:c.516G>C with confirmed maternity and paternity. Details ▾Hide ▴
Still missing
- No de novo confirmation data available.
PP1 No co-segregation data available. No family studies have been conducted for this variant. Details ▾Hide ▴
Still missing
- No family segregation data available.
PP2 IDH2 disease mechanism is predominantly gain-of-function/neomorphic via missense mutations at specific active site residues (R172, R140), not a gene where a low rate of benign missense variation and high missense constraint is the defining feature. The gene does not meet the typical PP2 profile of a gene where missense variants are a common mechanism of disease with low benign missense tolerance in population databases. Details ▾Hide ▴
Evidence considered
- IDH2 disease mechanism is neomorphic gain-of-function
- not loss-of-function via random missense variation.
- Specific residues (R172
- R140) are hotspots
- not all missense variants in IDH2 are pathogenic.
PP3 In silico predictions are mixed and do not provide multiple lines of computational support for a deleterious effect. REVEL score is 0.567 (moderate, below the typical damaging threshold of >0.7). BayesDel score is 0.31655 (low, not predicted damaging). SpliceAI max delta is 0.01 (no predicted splice impact). Only one tool (REVEL) shows moderate evidence, which is insufficient for PP3. Details ▾Hide ▴
Evidence considered
- REVEL: 0.567 (moderate
- below damaging threshold).
- BayesDel: 0.31655 (not damaging).
- SpliceAI: max delta 0.01 (no splice impact).
Sources
PP4 No patient phenotype or clinical data available for this variant. The ClinVar submission is of somatic origin (risk factor) and provides no germline phenotype information. Details ▾Hide ▴
Still missing
- No germline patient phenotype data available.
PP5 ClinVar classification for this variant (VariationID 375985) is risk factor with review status 'no assertion criteria provided' (0-star). PP5 requires a reputable source with 3-star expert panel review to be applied at supporting strength. The single ClinVar submission (SCV002047547) is from a non-clinical testing source without assertion criteria, and does not qualify for PP5. Details ▾Hide ▴
Evidence considered
- ClinVar VariationID 375985: risk factor
- 0-star review
- no assertion criteria provided.
- Single submission: SCV002047547
- Clinical Pathology Tanta University
- somatic origin
- case-control method.
Still missing
- No 3-star expert panel ClinVar classification available.
Sources
BA1 Variant allele frequency in gnomAD v4.1 is 6.19 × 10⁻⁷ (0.00006%), far below the BA1 threshold of >1%. Variant is absent from gnomAD v2.1. Details ▾Hide ▴
BS1 Variant allele frequency in gnomAD v4.1 is 6.19 × 10⁻⁷ (0.00006%), far below the BS1 threshold of >0.3%. Details ▾Hide ▴
BS2 No data on observation of this variant in healthy adults. The single gnomAD allele (1/1,614,224) is insufficient to establish BS2, as a single observation does not confirm healthy adult status. Details ▾Hide ▴
Still missing
- No data on healthy adult carriers.
BS3 Well-established functional studies (PMID:20171147, PMID:23264629) demonstrate that IDH2 R172 mutations produce a neomorphic gain-of-function — converting α-ketoglutarate to the oncometabolite 2-hydroxyglutarate — rather than showing no damaging effect. The literature does not support a benign functional interpretation for IDH2 R172 mutations. Details ▾Hide ▴
Evidence considered
- IDH2 R172 mutants exhibit neomorphic gain-of-function producing 2HG
- not a benign functional effect.
Sources
BS4 No segregation data available to demonstrate lack of co-segregation with disease. Details ▾Hide ▴
Still missing
- No family segregation data available.
BP1 IDH2 disease mechanism is predominantly gain-of-function/neomorphic via specific missense mutations at active site residues. BP1 applies to genes where primarily truncating variants cause disease and missense variants are less likely to be pathogenic. IDH2 does not fit this profile; the known pathogenic mechanism is missense-based neomorphic activity. Details ▾Hide ▴
Evidence considered
- IDH2 pathogenic mechanism is missense-based neomorphic gain-of-function
- not truncating loss-of-function.
BP2 No data on observation in trans with a pathogenic variant. The variant is extremely rare and no trans configuration data exists. Details ▾Hide ▴
Still missing
- No trans configuration data available.
BP4 Computational evidence does not support a benign interpretation. REVEL score is 0.567 (moderate, not clearly benign), BayesDel is 0.31655, and SpliceAI shows no splice impact. The in silico evidence is mixed and does not provide multiple lines of evidence suggesting no impact. Details ▾Hide ▴
Evidence considered
- REVEL 0.567: moderate
- not clearly benign.
- BayesDel 0.31655: low but not definitive for benign.
- SpliceAI max delta 0.01: no splice impact.
Sources
BP5 No data indicating this variant is found in a case with an alternate molecular basis for disease. Details ▾Hide ▴
Still missing
- No alternate molecular basis data available.
BP6 ClinVar classification is risk factor, not benign. Review status is 'no assertion criteria provided' (0-star). BP6 requires a reputable source classifying the variant as benign with strong supporting evidence. The available ClinVar entry does not meet this threshold. Details ▾Hide ▴
Evidence considered
- ClinVar VariationID 375985: risk factor
- not benign. 0-star review.
Sources
Not applicable · 4· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_002168.3:c.516G>C is a missense variant (p.Arg172Ser); it does not fall into the generic PVS1 null-variant buckets (nonsense, frameshift, or canonical ±1,2 splice consensus variants). PVS1 is not applicable to missense variants under the ClinGen SVI PVS1 framework (PMC6185798). Details ▾Hide ▴
Evidence considered
- Missense variant
- variant_bucket: other
- apply_generic_pvs1_framework: false.
Sources
BP3 N/ANM_002168.3:c.516G>C is a single-nucleotide substitution (missense), not an in-frame deletion or insertion in a repetitive region. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ANM_002168.3:c.516G>C is a missense variant (p.Arg172Ser), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
No further detail was recorded.
PS5 N/APS5 applies when two pathogenic variants are observed in trans for recessive disorders. No recessive disease context has been established for IDH2, and no trans configuration data exists. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- IDH2
- Transcript
- NM_002168.3
- Coding (HGVS c.)
- NM_002168.3:c.516G>C
- Protein (HGVS p.)
- NP_002159.2:p.(Arg172Ser)
- GRCh38
- chr15:90088605 C>G
- GRCh37
- chr15:90631837 C>G
- ClinVar
- 375985
- COSMIC
- COSV57468772
Gene diagram
Every interpreted variant in IDH2, mapped onto the exon structure of NM_002168.3. Select a row to find it on the plot.
IDH2NM_002168.3
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 IDH2
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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
1 / 1,614,224 alleles
AF 6.19e-07 · 0 homozygotes
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 6.2e-07 · 1 / 1,614,224 alleles · 0 hom
| Ashkenazi Jewish1 / 29,606 | 3.4e-05 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, African/African American, European (non-Finnish).
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 6.19493e-07; MAF= 0.00006%, 1/1614224 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 3.37769e-05; MAF= 0.00338%, 1/29606 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.567
- BayesDel
- 0.317
How the predictions were used
PP3 In silico predictions are mixed and do not provide multiple lines of computational support for a deleterious effect. REVEL score is 0.567 (moderate, below the typical damaging threshold of >0.7). BayesDel score is 0.31655 (low, not predicted damaging). SpliceAI max delta is 0.01 (no predicted splice impact). Only one tool (REVEL) shows moderate evidence, which is insufficient for PP3. Details ▾Hide ▴
Evidence considered
- REVEL: 0.567 (moderate
- below damaging threshold).
- BayesDel: 0.31655 (not damaging).
- SpliceAI: max delta 0.01 (no splice impact).
Sources
BP4 Computational evidence does not support a benign interpretation. REVEL score is 0.567 (moderate, not clearly benign), BayesDel is 0.31655, and SpliceAI shows no splice impact. The in silico evidence is mixed and does not provide multiple lines of evidence suggesting no impact. Details ▾Hide ▴
Evidence considered
- REVEL 0.567: moderate
- not clearly benign.
- BayesDel 0.31655: low but not definitive for benign.
- SpliceAI max delta 0.01: no splice impact.
Sources
BP7 N/ANM_002168.3:c.516G>C is a missense variant (p.Arg172Ser), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.567. BayesDel score = 0.31655.
5 paper records listed. 1 cited in the classification.
Cited in the classification
-
PMID 24403254 ↗Isocitrate dehydrogenase 2 mutation is a frequent event in osteosarcoma detected by a multi-specific monoclonal antibody MsMab-1.Identified IDH2-R172S in 3 of 12 (25%) osteosarcoma patients by direct DNA sequencing (AGG>AGT). Developed and validated MsMab-1 multi-specific monoclonal antibody that detects IDH2-R172S by ELISA, Western blot, and immunohistochemistry. No morphological difference, growth difference, or cell migration difference was observed between IDH2-WT and IDH2-R172S transfected U-2 OS osteosarcoma cells at 2 days post-transfection. MsMab-1 stained 9 of 32 (28.1%) osteosarcomas on tissue microarray.→ PM1 Names this variant
Source detail
This article describes the IDH2-R172S mutation in 3 of 12 (25%) osteosarcoma patients, which was detected by direct DNA sequencing. Furthermore, MsMab-1 stained nine of 32 (28.1%) osteosarcomas in a tissue microarray.
Location Introduction (describes R172S in osteosarcoma); Results, Mutational analysis section (3/12 patients, Fig 1); Results, Specificity of MsMab-1 section (ELISA Tables 3-4, Western blot Fig 2); Results, Immunohistochemical analysis (Fig 3); Discussion paragraphs 1-3.
Context Direct DNA sequencing of osteosarcoma FFPE tissue; ELISA with synthetic IDH2 peptides; Western blot using CHO and U-2 OS cells transfected with IDH2-R172S; immunohistochemistry on osteosarcoma tissue microarray
Other recorded publications
-
PMID 20171147 ↗The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate.Characterized the neomorphic enzyme activity of IDH2 R172 mutants, demonstrating that IDH2 R172 mutations confer a gain-of-function for NADPH-dependent reduction of α-ketoglutarate to the oncometabolite (R)-2-hydroxyglutarate (2HG). Specifically tested IDH2-R172K; NM_002168.3:c.516G>C (p.Arg172Ser) was not identified or characterized in this paper.Does not name this variant
Quoted passage
The IDH2 mutations which have been identified in gliomas occur at the analogous residue to IDH1 R132, IDH2 R172. Both IDH1 R132 and IDH2 R172 mutants lack the wild-type enzyme's ability to convert isocitrate to α-ketoglutarate.
Introduction paragraph 1; describes IDH2 R172 as the analogous residue to IDH1 R132. Results tested R172K specifically.
-
PMID 20567020 ↗IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication.Analyzed frequency and prognostic impact of IDH1 and IDH2 mutations in 805 adults with acute myeloid leukemia. Reported IDH2 mutations at R140 and R172 in AML but did not specifically identify or characterize NM_002168.3:c.516G>C (p.Arg172Ser).Does not name this variant
-
PMID 23264629 ↗The potential for isocitrate dehydrogenase mutations to produce 2-hydroxyglutarate depends on allele specificity and subcellular compartmentalization.Demonstrated that cellular 2HG production from mitochondrial IDH2 mutations is independent of wild-type IDH2 allele activity, in contrast to cytosolic IDH1 mutations. Discussed IDH2 R172 mutations generally but did not specifically study NM_002168.3:c.516G>C (p.Arg172Ser).Does not name this variant
-
PMID 28193778 ↗AG-221, a First-in-Class Therapy Targeting Acute Myeloid Leukemia Harboring Oncogenic IDH2 Mutations.Described AG-221 (enasidenib), a first-in-class small molecule inhibitor targeting oncogenic IDH2 mutations in acute myeloid leukemia. Discussed IDH2 R140Q and R172K as the primary targets but did not specifically study or characterize NM_002168.3:c.516G>C (p.Arg172Ser).Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
1 / 1,614,224 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
Captured ClinVar source record
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/375985/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/15-90631837-C-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr15-90088605-C-G?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/15-90088605-C-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_002168.3%3Ac.516G…
- OncoKB ↗www.oncokb.org/gene/IDH2/R172S
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=131225402
- 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= 6.19493e-07; MAF= 0.00006%, 1/1614224 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 3.37769e-05; MAF= 0.00338%, 1/29606 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar but submission details could not be extracted. (ClinVarID = 375985)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.567. BayesDel score = 0.31655.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; curated oncogenicity label: Oncogenic.
Somatic
This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV57468772, n = 35 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.