About IDH1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
IDH1 c.394C>A, p.Arg132Ser
Classification
Likely pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.
Likely pathogenic.A likely pathogenic 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 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: 5
Benign evidence criteria: 0
Pathogenic criteria applied · 5
PS3Moderate
PS3 · moderate
The IDH1 R132S variant was directly tested in recombinant protein functional assays. Dang et al. (2009) generated purified recombinant R132S mutant IDH1 protein and demonstrated that R132S, like other R132 mutations, results in gain-of-function NADPH-dependent reduction of α-ketoglutarate to the oncometabolite (R)-2-hydroxyglutarate. The functional effect is unequivocal: the mutation alters enzymatic activity from oxidative decarboxylation of isocitrate to reductive production of 2-HG. A single study with direct variant-specific testing supports moderate-strength PS3.
PM1Moderate
PM1 · moderate
The variant alters Arg132, the critical active-site residue of IDH1 responsible for isocitrate substrate binding and catalysis. This residue is located in the enzyme's catalytic domain and is a statistically significant mutational hotspot (cancerhotspots.org). All known oncogenic IDH1 mutations occur at this residue. The Arg132 position forms hydrogen bonds with the α- and β-carboxyl groups of isocitrate and is essential for normal enzymatic function.
PM2Moderate
PM2 · moderate
This variant is completely absent from population databases. gnomAD v4.1 reports 0 alleles in 1,613,196 alleles across all populations (AF=0.000%). gnomAD v2.1 and gnomAD-Canada v1.0 also report complete absence. The allele frequency is well below the 0.1% threshold for PM2 under generic ACMG rules.
PM5Moderate
PM5 · moderate
A different missense change at the same amino acid residue (p.Arg132) has been established as pathogenic. IDH1 p.Arg132His (R132H) is the most common and well-characterized pathogenic IDH1 variant in gliomas and other cancers. p.Arg132Cys (R132C) is also established as pathogenic. Both are listed as pathogenic in ClinVar and extensively characterized in the literature. The current variant, p.Arg132Ser, is a different amino acid change at the same residue.
PP3Supporting
PP3 · supporting
Multiple in silico tools support a deleterious effect. REVEL score is 0.904 (strongly pathogenic prediction). SpliceAI predicts a possible splice impact with a maximum delta score of 0.61 (donor gain delta = 0.61, donor loss delta = 0.48). BayesDel score is 0.419 (moderate). The high REVEL score and moderate SpliceAI signal together provide supporting evidence for a deleterious effect.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Likely pathogenic
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PS3 moderate, PM1 moderate, PM2 moderate, PM5 moderate, PP3 supporting; combination = 4 moderate + 1 supporting, which maps to Likely Pathogenic.
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
0 / 1,613,196 alleles
gnomAD v4.1: 0 / 1,613,196 alleles. Recorded AF 0. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.610 maximum delta
Recorded SpliceAI maximum delta score: 0.610. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
1 reported laboratory submissions
1 Pathogenic. 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; curated oncogenicity label: Likely Oncogenic.
COSMIC
Cancer Hotspots
Somatic evidence
217 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV61615649, n = 217 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.
29 criteria with recorded statuses: 5 met · 17 not met · 2 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
IDH1 c.394C>A (p.Arg132Ser) is absent from population databases (gnomAD v4.1: 0/1,613,196 alleles).
The variant alters the critical active-site residue Arg132 of IDH1, a well-established mutational hotspot and functional domain essential for substrate binding and catalysis.
Different missense changes at the same residue (p.Arg132His, p.Arg132Cys) are established pathogenic variants, satisfying PM5.
Functional studies directly testing the R132S mutant protein demonstrate neomorphic gain-of-function activity: NADPH-dependent reduction of α-ketoglutarate to the oncometabolite (R)-2-hydroxyglutarate.
Multiple in silico tools support a deleterious effect, including a REVEL score of 0.904 and a SpliceAI max delta of 0.61.
ClinVar reports this variant as Pathogenic (VariationID 375893) based on a single clinical laboratory submission with criteria provided (1-star). This does not reach the 3-star expert panel threshold required for PP5.
The variant has been reported in somatic cancers (COSMIC: n=217), primary myelofibrosis (3/301 patients; PMID:21912393), and a case of adult medulloblastoma (PMID:24616312), consistent with oncogenicity but not meeting germline PS4 thresholds.
No criteria match.
Met · 5
PS3 ModerateThe IDH1 R132S variant was directly tested in recombinant protein functional assays. Dang et al. (2009) generated purified recombinant R132S mutant IDH1 protein and demonstrated that R132S, like other R132 mutations, results in gain-of-function NADPH-dependent reduction of α-ketoglutarate to the oncometabolite (R)-2-hydroxyglutarate. The functional effect is unequivocal: the mutation alters enzymatic activity from oxidative decarboxylation of isocitrate to reductive production of 2-HG. A single study with direct variant-specific testing supports moderate-strength PS3. Details ▾Hide ▴
Evidence considered
- R132S mutant IDH1 protein directly tested in recombinant enzyme assays
- R132S demonstrated gain-of-function: NADPH-dependent reduction of αKG to (R)-2-hydroxyglutarate
- Functional effect unequivocal — loss of normal isocitrate decarboxylation
- gain of neomorphic 2-HG production
Still missing
- Single study only
- second independent functional confirmation would strengthen to strong
- Functional data derived from somatic cancer context
- germline-specific functional studies not available
Sources
PM1 ModerateThe variant alters Arg132, the critical active-site residue of IDH1 responsible for isocitrate substrate binding and catalysis. This residue is located in the enzyme's catalytic domain and is a statistically significant mutational hotspot (cancerhotspots.org). All known oncogenic IDH1 mutations occur at this residue. The Arg132 position forms hydrogen bonds with the α- and β-carboxyl groups of isocitrate and is essential for normal enzymatic function. Details ▾Hide ▴
Evidence considered
- Arg132 is the enzyme active-site residue critical for isocitrate binding and catalysis
- Residue-level statistical significance confirmed at cancerhotspots.org
- All known oncogenic IDH1 mutations cluster at Arg132 (R132H
- R132C
- R132L
- R132S
- R132G)
Sources
PM2 ModerateThis variant is completely absent from population databases. gnomAD v4.1 reports 0 alleles in 1,613,196 alleles across all populations (AF=0.000%). gnomAD v2.1 and gnomAD-Canada v1.0 also report complete absence. The allele frequency is well below the 0.1% threshold for PM2 under generic ACMG rules. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 0/1
- 613
- 196 alleles (AF=0.000%)
- gnomAD v2.1: absent
- gnomAD-Canada v1.0: absent
Sources
PM5 ModerateA different missense change at the same amino acid residue (p.Arg132) has been established as pathogenic. IDH1 p.Arg132His (R132H) is the most common and well-characterized pathogenic IDH1 variant in gliomas and other cancers. p.Arg132Cys (R132C) is also established as pathogenic. Both are listed as pathogenic in ClinVar and extensively characterized in the literature. The current variant, p.Arg132Ser, is a different amino acid change at the same residue. Details ▾Hide ▴
Evidence considered
- IDH1 p.Arg132His (R132H) is an established pathogenic variant
- IDH1 p.Arg132Cys (R132C) is an established pathogenic variant
- Both are different amino acid changes at the same residue as p.Arg132Ser
Sources
PP3 SupportingMultiple in silico tools support a deleterious effect. REVEL score is 0.904 (strongly pathogenic prediction). SpliceAI predicts a possible splice impact with a maximum delta score of 0.61 (donor gain delta = 0.61, donor loss delta = 0.48). BayesDel score is 0.419 (moderate). The high REVEL score and moderate SpliceAI signal together provide supporting evidence for a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.904 (strongly pathogenic)
- SpliceAI max delta: 0.61 (DG=0.61
- DL=0.48)
- suggesting possible splice impact
- BayesDel score: 0.419
Sources
Not met · 17 · evaluated, threshold not reached
PS1 No evidence of a different nucleotide change at this codon producing the same amino acid substitution (p.Arg132Ser) that has been previously classified as pathogenic. PS1 requires a different nucleotide change resulting in the identical amino acid change with an established pathogenic classification, which is not present in the available data. Details ▾Hide ▴
Evidence considered
- No alternate nucleotide change producing p.Arg132Ser identified in ClinVar or literature
PS2 No de novo data available for this variant. No report of de novo occurrence with confirmed maternity and paternity was found in ClinVar, the literature, or any other source. Details ▾Hide ▴
Still missing
- No de novo testing data available
PS4 No case-control comparison data available to demonstrate statistically significant increased prevalence of this variant in affected individuals versus controls. The variant has been observed in somatic cancers (COSMIC: 217 times) and in clinical cohorts (3/301 PMF patients in PMID:21912393, 1 case of adult medulloblastoma in PMID:24616312), but these are somatic observations and do not constitute germline case-control evidence for PS4. Details ▾Hide ▴
Evidence considered
- Observed in COSMIC (n=217
- somatic)
- Observed in 3/301 primary myelofibrosis patients (somatic)
- Observed in 1 adult medulloblastoma case (somatic)
Still missing
- No germline case-control study available
Sources
PM6 No de novo data available. PM6 requires confirmed de novo occurrence with both maternity and paternity confirmed. No such evidence was identified in ClinVar or the reviewed literature. Details ▾Hide ▴
Still missing
- No de novo testing data available
PP1 No co-segregation data available. No family studies demonstrating co-segregation of this variant with disease were identified. Details ▾Hide ▴
Still missing
- No family segregation data available
PP5 ClinVar reports this variant as Pathogenic with review status 'criteria provided, single submitter' (1 star). Under the current PP5 rule, only 3-star expert panel ClinVar submissions qualify for PP5 at supporting strength. The available ClinVar submission is from a single clinical laboratory (CeGaT Center for Human Genetics Tuebingen), not an expert panel. At 1-star review status, PP5 is not met. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Pathogenic (VariationID 375893)
- Review status: criteria provided
- single submitter (1 star)
- Single clinical laboratory submission
- not expert panel
Sources
BA1 This variant is absent from gnomAD v4.1 (0/1,613,196 alleles, AF=0.000%), well below the BA1 threshold of >1% allele frequency. It is not a common polymorphism. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 0/1
- 613
- 196 alleles (AF=0.000%)
- far below 1% BA1 threshold
Sources
BS1 This variant is absent from gnomAD v4.1 (0/1,613,196 alleles, AF=0.000%), well below the BS1 threshold of >0.3% allele frequency. It is not observed at a frequency consistent with a benign variant. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 0/1
- 613
- 196 alleles (AF=0.000%)
- far below 0.3% BS1 threshold
Sources
BS2 This variant has not been observed in healthy adult individuals. It is completely absent from gnomAD population databases. No evidence of observation in healthy controls exists. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD population databases (0/1
- 613
- 196 alleles)
- No reports of healthy individuals carrying this variant
Sources
BS3 Well-established functional studies demonstrate a damaging gain-of-function effect, not a benign effect. Dang et al. (2009) showed that R132S mutant IDH1 produces the oncometabolite (R)-2-hydroxyglutarate through neomorphic enzymatic activity. This functional evidence supports pathogenicity, not benign impact. Details ▾Hide ▴
Evidence considered
- R132S demonstrates gain-of-function: NADPH-dependent reduction of αKG to 2-HG
- Functional data support damaging effect
- not benign
Sources
BS4 No segregation data available. BS4 requires lack of segregation in affected family members, which cannot be assessed without family studies. Details ▾Hide ▴
Still missing
- No family segregation data available
BP1 IDH1 disease mechanism in cancer is primarily gain-of-function via missense mutations at Arg132. The gene is not characterized by a primary truncating variant disease mechanism. BP1 does not apply because IDH1 pathogenicity is mediated by missense changes at a critical functional residue, not by loss-of-function through truncation. Details ▾Hide ▴
Evidence considered
- IDH1 pathogenic mechanism is gain-of-function via missense at Arg132
- Truncating variants are not the established disease mechanism for IDH1
Sources
BP2 No data available regarding observation of this variant in trans with a pathogenic variant. No compound heterozygosity data exists for this variant. Details ▾Hide ▴
Still missing
- No data on trans configuration with pathogenic variants
BP4 Multiple in silico tools predict a deleterious effect, not a benign effect. REVEL score is 0.904 (strongly pathogenic). SpliceAI delta score is 0.61 (possible splice impact). These computational predictions support pathogenicity, not benign impact. Details ▾Hide ▴
Evidence considered
- REVEL: 0.904 (damaging prediction)
- SpliceAI max delta: 0.61 (possible splice-altering)
- Computational evidence supports deleterious effect
- not benign
Sources
BP5 ClinVar classifies this variant as Pathogenic, not benign. The single submission from a clinical laboratory reports the variant as Pathogenic. No reputable source classifies this variant as benign. Details ▾Hide ▴
BP6 ClinVar classifies this variant as Pathogenic, not benign. No reputable source reports this variant as benign. The single ClinVar submission reports Pathogenic with review status 'criteria provided, single submitter.' Details ▾Hide ▴
PS5 No segregation data available for this variant. No family studies or co-segregation analysis were identified in ClinVar or the reviewed literature. Details ▾Hide ▴
Still missing
- No family segregation data available
Not assessed · 2 · no assessment recorded
PP2 Insufficient data to assess the missense constraint profile of IDH1 for germline disease. HCI prior score is not available for IDH1. While IDH1 is known for recurrent somatic missense mutations in cancer, the gene-level missense constraint metrics for germline disease are not established in the available data. Details ▾Hide ▴
Evidence considered
- HCI prior not available for IDH1
- IDH1 missense constraint for germline disease not established
Still missing
- Missense constraint metrics (Z-score
- gnomAD missense constraint) not available
PP4 No specific patient phenotype or clinical information was provided for this case. PP4 requires that the patient's phenotype or family history is highly specific for a disease with a single genetic etiology. Without phenotype data, PP4 cannot be assessed. Details ▾Hide ▴
Still missing
- Patient phenotype and clinical history not provided
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis is a missense variant (c.394C>A, p.Arg132Ser). It does not fall into the default generic PVS1 null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants. The generic PVS1 framework assessment indicates 'apply_generic_pvs1_framework: false' and variant_bucket is 'other'. Details ▾Hide ▴
Evidence considered
- Missense variant not eligible for PVS1 null-variant framework per ClinGen SVI PVS1 recommendations (PMC6185798)
Sources
pvs1_variant_assessmentpvs1_generic_framework ↗
PM3 N/ANo evidence of recessive inheritance for IDH1-associated disease. PM3 requires observation in trans with a pathogenic variant for recessive disorders. Details ▾Hide ▴
No further detail was recorded.
PM4 N/AThis is a substitution variant, not an in-frame deletion or insertion. PM4 applies only to protein length-altering variants. Details ▾Hide ▴
No further detail was recorded.
BP3 N/AThis is a substitution variant, not an in-frame deletion or insertion. BP3 applies to in-frame indels in repeat regions. Details ▾Hide ▴
No further detail was recorded.
BP7 N/AThis is a missense variant (p.Arg132Ser), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- IDH1
- Transcript
- NM_005896.3
- Coding (HGVS c.)
- NM_005896.3:c.394C>A
- Protein (HGVS p.)
- NP_005887.2:p.(Arg132Ser)
- GRCh38
- chr2:208248389 G>T
- GRCh37
- chr2:209113113 G>T
- ClinVar
- 375893, 156444
- COSMIC
- COSV61615649
Gene diagram
Every interpreted variant in IDH1, mapped onto the exon structure of NM_005896.3. Select a row to find it on the plot.
IDH1NM_005896.3
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 IDH1
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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
0 / 1,613,196 alleles
AF 0 · 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 0 · 0 / 1,613,196 alleles · 0 hom
No alternate alleles recorded in the displayed ancestry groups.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0; MAF= 0.00000%, 0/1613196 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/74792 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
- 0.904
- BayesDel
- 0.419
How the predictions were used
PP3 SupportingMultiple in silico tools support a deleterious effect. REVEL score is 0.904 (strongly pathogenic prediction). SpliceAI predicts a possible splice impact with a maximum delta score of 0.61 (donor gain delta = 0.61, donor loss delta = 0.48). BayesDel score is 0.419 (moderate). The high REVEL score and moderate SpliceAI signal together provide supporting evidence for a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.904 (strongly pathogenic)
- SpliceAI max delta: 0.61 (DG=0.61
- DL=0.48)
- suggesting possible splice impact
- BayesDel score: 0.419
Sources
BP4 Multiple in silico tools predict a deleterious effect, not a benign effect. REVEL score is 0.904 (strongly pathogenic). SpliceAI delta score is 0.61 (possible splice impact). These computational predictions support pathogenicity, not benign impact. Details ▾Hide ▴
Evidence considered
- REVEL: 0.904 (damaging prediction)
- SpliceAI max delta: 0.61 (possible splice-altering)
- Computational evidence supports deleterious effect
- not benign
Sources
BP7 N/AThis is a missense variant (p.Arg132Ser), 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 possible splice impact for this variant (max delta score = 0.61). REVEL score = 0.904. BayesDel score = 0.419369.
8 paper records listed. 2 cited in the classification.
Cited in the classification
-
PMID 19935646 ↗Cancer-associated IDH1 mutations produce 2-hydroxyglutarate.Dang L et al. · 2009 Dec 10IDH1 R132S was directly tested in recombinant protein functional assays. R132S mutant IDH1 demonstrated gain-of-function neomorphic activity: NADPH-dependent reduction of α-ketoglutarate to the oncometabolite (R)-2-hydroxyglutarate (2-HG), while losing normal isocitrate decarboxylation activity. This functional effect was shared with R132H, R132C, and R132L mutations.→ PS3 → PM1 → PM5 Names this variant
Source detail
Similar to R132H mutant protein, R132C, R132L, and R132S mutations all result in a gain-of-function for NADPH-dependent reduction of αKG.
Location Results section; Supplementary Figure 4; Methods Summary
Context Recombinant protein purification from E. coli; stopped-flow spectrophotometry enzyme assays; LC-MS metabolite detection; U87MG and LN-18 glioblastoma cell lines
-
PMID 23630074 ↗What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer.Losman JA et al. · 2013 Apr 15This is a comprehensive review of IDH mutations in cancer. R132S is listed among the known IDH1 mutant alleles in tabular summaries of mutation frequencies across tumor types. The review summarizes the gain-of-function mechanism by which mutant IDH enzymes (including R132S) produce (R)-2-hydroxyglutarate, promoting tumorigenesis through epigenetic dysregulation.→ PM1 → PM5 Names this variant
Source detail
IDH1 R132C/S/L/G/V 5%-8%
Location Table 1 (allele frequencies); text describing IDH1 R132C/S/L/G/V mutant alleles
Context Review article; no primary experimental data
Other recorded publications
-
PMID 21760534 ↗Value and limitations of immunohistochemistry and gene sequencing for detection of the IDH1-R132H mutation in diffuse glioma biopsy specimens.No paper-specific finding is recorded.
-
PMID 21912393 ↗IDH mutations in primary myelofibrosis predict leukemic transformation and shortened survival: clinical evidence for leukemogenic collaboration with JAK2V617F.In a cohort of 301 consecutive patients with chronic-phase primary myelofibrosis (PMF), IDH mutations were detected in 12 patients (4%): 7 IDH2 and 5 IDH1 (3 R132S and 2 R132C). IDH-mutated patients had significantly shorter overall survival and leukemia-free survival. Concomitant IDH1 R132S and JAK2 V617F was associated with a particularly high risk of leukemic transformation.Names this variant
Quoted passage
The mutant IDH was detected in 12 patients (4%): 7 IDH2 (5 R140Q, 1 R140W and 1 R172G) and 5 IDH1 (3 R132S and 2 R132C).
Results, paragraph 1; Discussion
-
PMID 22033490 ↗Differential prognostic effect of IDH1 versus IDH2 mutations in myelodysplastic syndromes: a Mayo Clinic study of 277 patients.No paper-specific finding is recorded.
-
PMID 22918138 ↗Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.Schrijver I et al. · 2012This is an Association for Molecular Pathology report on clinical diagnostic genome sequencing opportunities and challenges. It discusses NGS technologies, clinical applications, and ethical considerations. IDH1 c.394C>A (p.Arg132Ser) was not mentioned or discussed in this paper.Does not name this variant
-
PMID 24616312 ↗Deep sequencing identifies IDH1 R132S mutation in adult medulloblastoma.Snuderl M et al. · 2015A 62-year-old woman with adult medulloblastoma was found to harbor a heterozygous IDH1 c.394C>A (R132S) mutation by deep amplicon sequencing. Both tumor specimens (biopsy and resection) contained the R132S mutation. This represents the first report of IDH1 R132S in adult medulloblastoma, suggesting IDH1 mutations may play a role in adult medulloblastoma tumorigenesis.Names this variant
Quoted passage
Both M3 and M13 samples contained a heterozygous IDH1 CGT>AGT R132S mutation.
Results, paragraph describing deep sequencing findings; Figure 3
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PMID 23619274 ↗American College of Medical Genetics and Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in neoplastic disorders.Cooley LD et al. · 2013No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
0 / 1,613,196 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.610
Open source ↗
ClinVar
1 Pathogenic
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/375893/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-209113113-G-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-208248389-G-T?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-208248389-G-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_005896.3%3Ac.394C…
- OncoKB ↗www.oncokb.org/gene/IDH1/R132S
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=153664028
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0; MAF= 0.00000%, 0/1613196 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/74792 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 as Pathogenic (1 clinical laboratory). (ClinVarID = 375893)
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.61). REVEL score = 0.904. BayesDel score = 0.419369.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV61615649, n = 217 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.