About TET2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
TET2 c.822del, p.(Asn275IlefsTer18)
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
PVS1Very strong
PVS1 · very strong
NM_001127208.2:c.822del is a frameshift variant in exon 3 of 11, predicted to cause a premature termination codon at position 292 (NP_001120680.1:p.(Asn275IlefsTer18)) with expected nonsense-mediated decay. TET2 has an established loss-of-function disease mechanism in the germline context, associated with an ALPS-like phenotype and hematologic malignancy susceptibility. Under ClinGen SVI PVS1 recommendations (PMC6185798), a null variant in a gene where LOF is a known mechanism of disease meets PVS1 at very strong strength.
PM2Supporting
PM2 · supporting
This variant is present in gnomAD at extremely low frequency (v2.1: AF=0.0016%, 4/250,288 alleles; v4.1: AF=0.00167%, 27/1,613,714 alleles; highest subpopulation AF=0.00327% in South Asian, gnomAD v2.1). This frequency is well below the 0.1% threshold for PM2 under generic ACMG/AMP rules. No homozygotes have been observed.
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: PVS1 very strong, PM2 supporting; combination = 1 very strong + 1 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
27 / 1,613,714 alleles
gnomAD v4.1: 27 / 1,613,714 alleles. Recorded AF 1.67316e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.59816e-05; MAF= 0.00160%, 4/250288 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.27097e-05; MAF= 0.00327%, 1/30572 alleles, homozygotes = 0); grpmax FAF= 2.94e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
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
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; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
30 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV54404867, n = 30 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.
28 criteria with recorded statuses: 2 met · 22 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
NM_001127208.2:c.822del is a frameshift deletion in exon 3 of TET2, predicted to cause a premature termination codon (p.Asn275IlefsTer18) with expected nonsense-mediated decay, meeting PVS1 at very strong strength. TET2 loss-of-function is an established germline disease mechanism associated with ALPS-like phenotype and hematologic malignancy susceptibility.
This variant is present in gnomAD at extremely low frequency (AF=0.00167% in v4.1, 0.00160% in v2.1; no homozygotes), meeting PM2 at supporting strength.
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00), but REVEL and BayesDel are not available for this deletion variant, so PP3 is not met.
This variant has been reported as Pathogenic in ClinVar by a single clinical laboratory (1-star review status). PP5 requires a 3-star expert panel review and is not met. The variant is absent from COSMIC as a somatic observation? No: COSMIC reports this variant in n=30 somatic cancer samples (COSV54404867). OncoKB classifies the variant as Likely Oncogenic with Likely Loss-of-function effect.
No criteria match.
Met · 2
PVS1 Very strongNM_001127208.2:c.822del is a frameshift variant in exon 3 of 11, predicted to cause a premature termination codon at position 292 (NP_001120680.1:p.(Asn275IlefsTer18)) with expected nonsense-mediated decay. TET2 has an established loss-of-function disease mechanism in the germline context, associated with an ALPS-like phenotype and hematologic malignancy susceptibility. Under ClinGen SVI PVS1 recommendations (PMC6185798), a null variant in a gene where LOF is a known mechanism of disease meets PVS1 at very strong strength. Details ▾Hide ▴
Evidence considered
- Frameshift variant creating premature termination codon at p.Asn275IlefsTer18 in exon 3 of 11
- PTC is >50-55 nucleotides upstream of the next exon-exon junction (exon 3 is large: c.-46 to c.3409)
- NMD expected
- TET2 germline loss-of-function mechanism is supported by published literature associating germline TET2 mutations with ALPS-like phenotype and hematologic malignancy (PMID:36066697
- PMID:40031954)
- ClinGen SVI PVS1 Decision Tree (PMC6185798): frameshift variant
- LOF mechanism established
- NMD expected → PVS1
Sources
PM2 SupportingThis variant is present in gnomAD at extremely low frequency (v2.1: AF=0.0016%, 4/250,288 alleles; v4.1: AF=0.00167%, 27/1,613,714 alleles; highest subpopulation AF=0.00327% in South Asian, gnomAD v2.1). This frequency is well below the 0.1% threshold for PM2 under generic ACMG/AMP rules. No homozygotes have been observed. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=1.598e-05 (4/250
- 288 alleles
- 0 homozygotes)
- grpmax FAF=2.94e-06
- gnomAD v4.1: AF=1.673e-05 (27/1
- 613
- 714 alleles
- grpmax FAF=1.107e-05
- Highest subpopulation AF: 3.27e-05 (South Asian
- gnomAD v2.1)
- All AF values << 0.1% PM2 threshold
Sources
Not met · 22 · evaluated, threshold not reached
PS2 PS2 requires a confirmed de novo occurrence with both maternity and paternity confirmed. No de novo data are available for this variant. Details ▾Hide ▴
Still missing
- No de novo testing data available
PS3 PS3 requires variant-specific functional evidence. Two TET2 functional studies were reviewed in full text (PMID:21057493, PMID:24315485); neither tested c.822del or a systematically characterized range that includes codon 275. These papers demonstrate that TET2 catalytic domain mutations impair 5mC oxidation, but domain-level inference from sparse mutagenesis does not satisfy PS3's requirement for direct variant testing or systematic range characterization. The functional consequence of this frameshift variant is inferred from its null nature (PVS1), not from experimental data. Details ▾Hide ▴
Evidence considered
- Two TET2 functional studies were reviewed in full text (PMID:21057493
- PMID:24315485)
- neither tested c.822del or a systematically characterized range that includes codon 275
- PMID:21057493 tested only missense mutations in the catalytic domain
- PMID:24315485 characterized the catalytic domain structure (aa 1129-1936)
- not N-terminal positions
Still missing
- No variant-specific functional assay data for NM_001127208.2:c.822del nor for a systematically characterized range that includes codon 275
PS4 PS4 requires the variant prevalence in affected individuals to be significantly increased compared to controls. The variant has been reported in ClinVar by a single clinical laboratory (Invitae) as Pathogenic, and PMID:36066697 reports germline TET2 mutations in two patients with ALPS-like phenotype, but the abstract does not specify whether c.822del is among the variants described. Full text of PMID:36066697 is not available for confirmation. Without access to case-level data or case-control statistics, PS4 cannot be met. Details ▾Hide ▴
Evidence considered
- ClinVar: Classified Pathogenic by 1 submitter (Invitae)
- variation ID 1936676
- PS4 requires case-control prevalence data
- a single ClinVar submission without published case-level data is insufficient
- PMID:36066697 reports two patients with germline TET2 mutations but the abstract does not specify the variants
- full text not available to confirm whether c.822del is among them
Still missing
- PMID:36066697 full text not available
- cannot confirm whether c.822del is one of the reported variants
- No case-control prevalence data
Sources
PM1 PM1 requires location in a critical functional domain or mutational hotspot. The variant causes a frameshift at codon 275 in the N-terminal region of TET2, well upstream of the catalytic domain (aa 1129-1936). The variant creates a PTC with expected NMD, so the mechanism is complete loss of protein expression rather than domain-specific disruption. The codon 275 position is not in a statistically significant mutational hotspot (cancerhotspots.org) and is not within a characterized functional domain. The loss-of-function effect is already captured by PVS1. Details ▾Hide ▴
Evidence considered
- Cancer Hotspots: Residue not significant
- exact variant not listed
- PMID:24315485 crystal structure: TET2 catalytic domain spans residues 1129-1936
- codon 275 is in the N-terminal region outside any characterized functional domain
- The variant triggers NMD
- no truncated protein with domain loss is expected
PM6 PM6 requires an assumed de novo occurrence without confirmation of paternity and maternity. No de novo data are available for this variant. Details ▾Hide ▴
Still missing
- No de novo testing data available
PP1 PP1 requires co-segregation of the variant with disease in multiple affected family members. No segregation data are available for this variant. Details ▾Hide ▴
Still missing
- No family segregation data available
PP2 PP2 applies to missense variants in genes where missense variation is the primary pathogenic mechanism and benign missense variation is rare. TET2 disease mechanism is loss-of-function via truncating variants, and this variant is itself a frameshift deletion, not a missense substitution. PP2 does not apply. Details ▾Hide ▴
Evidence considered
- TET2 disease mechanism is LOF (truncating variants)
- not primarily missense
- This variant is a frameshift
- not a missense
PP3 PP3 requires multiple lines of computational evidence supporting a deleterious effect. REVEL and BayesDel scores are not available for this deletion variant. SpliceAI predicts no significant splice impact (max delta score = 0.00). The HCI prior is not available for TET2. No multiple lines of in silico evidence are available. Details ▾Hide ▴
Evidence considered
- SpliceAI: max delta score = 0.00 (no splice impact predicted)
- REVEL/BayesDel: not applicable (indel
- not SNV)
- HCI prior: gene not supported
Still missing
- In silico missense predictors not applicable to frameshift variants
Sources
PP4 PP4 requires a patient phenotype or family history highly specific for a disease with a single genetic etiology. No patient phenotype or family history data are available in this case. Details ▾Hide ▴
Still missing
- No patient phenotype data provided
PP5 PP5 requires a reputable source to have classified the variant as pathogenic with supporting evidence. This variant is classified as Pathogenic in ClinVar (variation ID 1936676) by a single clinical laboratory (Invitae) with review status 'criteria provided, single submitter' (1-star). Under the adjudication framework, PP5 at supporting strength requires a ClinVar 3-star expert panel review status, which is not met. Details ▾Hide ▴
Evidence considered
- ClinVar variation ID: 1936676
- Classification: Pathogenic (1 submitter)
- Review status: criteria provided
- single submitter (1-star)
- Insufficient star rating for PP5 under the 3-star EP threshold
Sources
BA1 BA1 requires an allele frequency >1% in population databases. This variant has a maximum population AF of 0.00327% in the South Asian population (gnomAD v2.1), and an overall AF of 0.0016-0.0017%, far below the 1% threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 overall AF: 0.00160% (well below 1%)
- gnomAD v4.1 overall AF: 0.00167% (well below 1%)
- Maximum subpopulation AF: 0.00327% (South Asian
- gnomAD v2.1)
Sources
BS1 BS1 requires an allele frequency >0.3% in population databases. This variant has a maximum population AF of 0.00327%, well below the 0.3% threshold. Details ▾Hide ▴
Evidence considered
- Maximum subpopulation AF: 0.00327% (well below 0.3%)
- Overall AF: 0.0016%-0.0017%
Sources
BS2 BS2 requires observation of the variant in a healthy adult individual for a disorder with full penetrance expected at an early age, in the appropriate zygosity state. No such observation data are available. Details ▾Hide ▴
Still missing
- No healthy adult observation data for TET2-related disease
BS3 BS3 requires well-established functional studies showing no damaging effect. The available functional literature (PMID:21057493, PMID:24315485) demonstrates that TET2 mutations impair catalytic function, and OncoKB classifies this variant as Likely Loss-of-function. No studies suggest a benign functional effect. Details ▾Hide ▴
Evidence considered
- OncoKB classification: Likely Loss-of-function
- Likely Oncogenic (based on variant type
- not direct experimental data)
- PMID:21057493 and PMID:24315485 demonstrate that TET2 catalytic domain missense mutations are damaging
- not benign
- neither paper tests a frameshift variant
- No functional study was identified that demonstrates a benign effect for any TET2 LOF variant
BS4 BS4 requires lack of segregation of the variant with disease in affected family members. No segregation data are available. Details ▾Hide ▴
Still missing
- No family segregation data available
BP1 BP1 applies to missense variants in genes where primarily truncating variants cause disease. This is itself a truncating (frameshift) variant, not a missense change. BP1 does not apply to the variant type it is designed to contrast against. Details ▾Hide ▴
Evidence considered
- This variant is a frameshift deletion (truncating)
- not a missense variant
BP2 BP2 requires observation of the variant in trans with a pathogenic variant for a fully penetrant dominant disorder, or in cis with a pathogenic variant in any inheritance pattern. No such data are available. Details ▾Hide ▴
Still missing
- No phase data available
BP3 BP3 applies to in-frame deletions or insertions in repetitive regions without known function. This variant is a frameshift deletion, not an in-frame change in a repetitive region. Details ▾Hide ▴
No further detail was recorded.
BP4 BP4 requires multiple lines of computational evidence suggesting no impact on the gene product. REVEL and BayesDel are not available for this deletion variant. SpliceAI shows no splice impact (max delta = 0.00), but this single line of evidence is insufficient for BP4. Additionally, the frameshift nature of the variant is inherently damaging and inconsistent with a benign computational prediction. Details ▾Hide ▴
Evidence considered
- SpliceAI: max delta = 0.00 (no splice impact)
- REVEL/BayesDel: not applicable (indel)
- Single line of computational evidence is insufficient for BP4
- frameshift variants are inherently damaging
Sources
BP5 BP5 requires the variant to be found in a case with an alternate molecular basis for disease. No such data are available. Details ▾Hide ▴
Still missing
- No data on alternate molecular diagnoses in carriers
BP6 BP6 requires a reputable source to have classified the variant as benign. This variant is classified as Pathogenic in ClinVar, not Benign. BP6 is not met. Details ▾Hide ▴
BP7 BP7 applies to synonymous variants with no predicted splice impact and low nucleotide conservation. This variant is a frameshift deletion, not a synonymous substitution. Details ▾Hide ▴
No further detail was recorded.
Not applicable · 4· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 applies to variants producing the same amino acid substitution as a known pathogenic missense change. This variant is a frameshift deletion, not an amino acid substitution. Details ▾Hide ▴
No further detail was recorded.
PM4 N/APM4 applies to non-repeat in-frame deletions/insertions or stop-loss variants causing protein length changes. This variant is a frameshift deletion, not an in-frame change. Details ▾Hide ▴
No further detail was recorded.
PM5 N/APM5 requires a novel missense variant at a residue where another missense change is known to be pathogenic. This is a frameshift variant; PM5 semantics cannot be applied. The pm5_candidates module confirmed this variant is not eligible for classic PM5 assessment. Details ▾Hide ▴
Evidence considered
- PM5 candidate harvesting confirmed variant is ineligible: frameshift
- not a missense substitution
Sources
pm5_candidates
PS5 N/APS5 applies to novel missense variants at a residue where a different missense change has been determined to be pathogenic. This variant is a frameshift deletion, not a missense variant. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- TET2
- Transcript
- NM_001127208.2
- Coding (HGVS c.)
- NM_001127208.2:c.822del
- Protein (HGVS p.)
- NP_001120680.1:p.(Asn275IlefsTer18)
- GRCh38
- chr4:105234763 TC>T
- GRCh37
- chr4:106155920 TC>T
- ClinVar
- 1936676
- COSMIC
- COSV54404867
Gene diagram
Every interpreted variant in TET2, mapped onto the exon structure of NM_001127208.2. Select a row to find it on the plot.
TET2NM_001127208.2
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 TET2
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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
27 / 1,613,714 alleles
AF 1.67e-05 · 0 homozygotes · FAF 1.11e-05
gnomAD v2.1
4 / 250,288 alleles
AF 1.6e-05 · 0 homozygotes · FAF 2.94e-06
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.7e-05 · 27 / 1,613,714 alleles · 0 hom · FAF 1.1e-05
| Ashkenazi Jewish1 / 29,588 | 3.4e-05 |
| East Asian1 / 44,842 | 2.2e-05 |
| South Asian2 / 91,068 | 2.2e-05 |
| European (non-Finnish)20 / 1,179,890 | 1.7e-05 |
| Remaining individuals1 / 62,484 | 1.6e-05 |
| European (Finnish)1 / 64,006 | 1.6e-05 |
| African/African American1 / 74,906 | 1.3e-05 |
0 alternate alleles recorded in 3 other groups: Admixed American, Amish, Middle Eastern.
gnomAD v2.1
AF 1.6e-05 · 4 / 250,288 alleles · 0 hom · FAF 2.9e-06
| South Asian1 / 30,572 | 3.3e-05 |
| Admixed American1 / 34,468 | 2.9e-05 |
| European (non-Finnish)2 / 112,998 | 1.8e-05 |
0 alternate alleles recorded in 5 other groups: African/African American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.67316e-05; MAF= 0.00167%, 27/1613714 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 3.37975e-05; MAF= 0.00338%, 1/29588 alleles, homozygotes = 0); grpmax FAF= 1.107e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.59816e-05; MAF= 0.00160%, 4/250288 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.27097e-05; MAF= 0.00327%, 1/30572 alleles, homozygotes = 0); grpmax FAF= 2.94e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 PP3 requires multiple lines of computational evidence supporting a deleterious effect. REVEL and BayesDel scores are not available for this deletion variant. SpliceAI predicts no significant splice impact (max delta score = 0.00). The HCI prior is not available for TET2. No multiple lines of in silico evidence are available. Details ▾Hide ▴
Evidence considered
- SpliceAI: max delta score = 0.00 (no splice impact predicted)
- REVEL/BayesDel: not applicable (indel
- not SNV)
- HCI prior: gene not supported
Still missing
- In silico missense predictors not applicable to frameshift variants
Sources
BP4 BP4 requires multiple lines of computational evidence suggesting no impact on the gene product. REVEL and BayesDel are not available for this deletion variant. SpliceAI shows no splice impact (max delta = 0.00), but this single line of evidence is insufficient for BP4. Additionally, the frameshift nature of the variant is inherently damaging and inconsistent with a benign computational prediction. Details ▾Hide ▴
Evidence considered
- SpliceAI: max delta = 0.00 (no splice impact)
- REVEL/BayesDel: not applicable (indel)
- Single line of computational evidence is insufficient for BP4
- frameshift variants are inherently damaging
Sources
BP7 BP7 applies to synonymous variants with no predicted splice impact and low nucleotide conservation. This variant is a frameshift deletion, not a synonymous substitution. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
3 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
-
PMID 21057493 ↗Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2.Demonstrates that TET2 is a catalytically active 5-methylcytosine dioxygenase and that TET2 mutations identified in myeloid malignancies compromise catalytic activity, resulting in low 5hmC levels. Bone marrow samples from patients with TET2 mutations displayed uniformly low 5hmC. Specific tested mutations were missense substitutions in the catalytic domain (H1302Y, D1304A, H1802R, H1802Q, P1287S, W1211R, C1834D, R1817S/M).Does not name this variant
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PMID 24315485 ↗Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation.Presents the crystal structure of the human TET2 catalytic domain (residues 1129-1936) bound to methylated DNA at 2.02 Å resolution. Identifies critical residues for Fe(II) coordination (H1382, D1384, H1881), 2-OG binding (R1261, H1416, R1896, S1898), DNA interaction (W1291, M1293, Y1294, Y1295, K1299, R1302, S1303), and zinc coordination. Demonstrates that mutations at these residues impair or abolish catalytic activity. The low-complexity insert spans residues 1464-1843.Does not name this variant
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PMID 36066697 ↗Novel Germline TET2 Mutations in Two Unrelated Patients with Autoimmune Lymphoproliferative Syndrome-Like Phenotype and Hematologic Malignancy.López-Nevado M et al. · 2023Reports two unrelated patients with ALPS-like phenotype (chronic lymphoproliferation, splenomegaly, cytopenias, immune dysregulation, T-cell lymphoma) harboring germline TET2 mutations: one compound heterozygous patient (P1) with biallelic TET2 LOF mutations resulting in absent TET2 expression, and one monoallelic TET2 mutation carrier (P2). Both patients presented with T-cell lymphoma. The study supports TET2 germline LOF as a disease mechanism, but the abstract does not specify the exact 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
27 / 1,613,714 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
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/1936676/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/4-106155920-TC-T?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr4-105234763-TC-T?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/4-105234763-TC-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_001127208.2%3Ac.8…
- OncoKB ↗www.oncokb.org/gene/TET2/N275Ifs*18
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=194812986
- 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= 1.67316e-05; MAF= 0.00167%, 27/1613714 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 3.37975e-05; MAF= 0.00338%, 1/29588 alleles, homozygotes = 0); grpmax FAF= 1.107e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.59816e-05; MAF= 0.00160%, 4/250288 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.27097e-05; MAF= 0.00327%, 1/30572 alleles, homozygotes = 0); grpmax FAF= 2.94e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Pathogenic (1 clinical laboratory). (ClinVarID = 1936676)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV54404867, n = 30 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.