About ABL1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ABL1 c.1001C>T, p.(Thr334Ile)
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: 4
Benign evidence criteria: 0
Pathogenic criteria applied · 4
PS3Moderate
PS3 · moderate
Well-established in vitro functional studies demonstrate that the T315I (p.Thr334Ile) substitution in the ABL1 kinase domain disrupts imatinib/STI-571 binding. Reconstitution experiments in 293T cells (PMID:11423618) showed the T315I mutant retained kinase activity at all STI-571 concentrations tested, confirming drug resistance. Crystallographic and biochemical studies (PMID:25686603) demonstrated axitinib binds the T315I mutant in an active DFG-in conformation distinct from wild-type, with Ki=100 pM for the mutant versus 3,800 pM for wild-type. Multiple independent functional assays from two laboratories support a deleterious functional effect.
PM1Moderate
PM1 · moderate
The c.1001C>T (p.Thr334Ile) variant alters the gatekeeper residue (Thr315 in canonical numbering) located in the ATP-binding pocket of the ABL1 kinase domain. This is a critical functional domain of the tyrosine kinase where pathogenic missense variants cluster without benign variation. The ClinVar 3billion submission also applied PM1.
PM2Moderate
PM2 · moderate
The variant is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0 population databases (allele frequency 0.0%). Per non-VCEP generic ACMG thresholds, PM2 applies when a variant is absent or present at <0.1% in population databases.
PP3Supporting
PP3 · supporting
REVEL score of 0.587 exceeds the 0.5 threshold for deleterious prediction. BayesDel score of 0.237 provides additional in silico support. SpliceAI predicts no splicing impact (max delta 0.00), consistent with a missense variant whose pathogenic mechanism is at the protein level.
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, PP3 supporting; combination = 3 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
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
Absent from gnomAD v2.1.
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.
ClinVar submissions
2 reported laboratory submissions
1 Likely pathogenic · 1 association.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. ABL1, a tyrosine kinase, is frequently altered by chromosomal translocations in leukemia.
COSMIC
Cancer Hotspots
Somatic evidence
91 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV59323790, n = 91 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.
26 criteria with recorded statuses: 4 met · 12 not met · 6 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
This variant has not been observed in population databases (absent from gnomAD v2.1, v4.1, and Canada; PM2).
The c.1001C>T (p.Thr334Ile) substitution alters the gatekeeper residue in the ATP-binding pocket of the ABL1 kinase domain, a critical functional domain where pathogenic missense variants cluster without benign variation (PM1).
Well-established in vitro functional studies demonstrate that the T315I substitution disrupts imatinib/STI-571 binding to the ABL1 kinase. Reconstitution experiments showed the mutant retained kinase activity at all STI-571 concentrations (PMID:11423618), and crystallographic studies confirmed a distinct active conformation with differential inhibitor binding (PMID:25686603) (PS3).
REVEL in silico prediction score of 0.587 supports a deleterious effect on protein function (PP3).
Three moderate criteria (PM1, PM2, PS3) and one supporting criterion (PP3) are met. Per generic ACMG/AMP 2015 combination rules (PMID:25741868), 3 moderate criteria alone meet the threshold for Likely Pathogenic.
Note: The T315I substitution is established as a somatic drug-resistance mutation in BCR-ABL1-driven leukemias. Germline disease association for this specific variant has not been established; ABL1 germline disorders (CHDSKM, HADS) are associated with different residue substitutions. This assessment applies the generic ACMG/AMP framework to the variant irrespective of disease context.
No criteria match.
Met · 4
PS3 ModerateWell-established in vitro functional studies demonstrate that the T315I (p.Thr334Ile) substitution in the ABL1 kinase domain disrupts imatinib/STI-571 binding. Reconstitution experiments in 293T cells (PMID:11423618) showed the T315I mutant retained kinase activity at all STI-571 concentrations tested, confirming drug resistance. Crystallographic and biochemical studies (PMID:25686603) demonstrated axitinib binds the T315I mutant in an active DFG-in conformation distinct from wild-type, with Ki=100 pM for the mutant versus 3,800 pM for wild-type. Multiple independent functional assays from two laboratories support a deleterious functional effect. Details ▾Hide ▴
Evidence considered
- T315I mutant BCR-ABL retained phosphorylation activity at all STI-571 concentrations in 293T reconstitution assay (PMID:11423618)
- Crystal structure of axitinib-ABL1(T315I) complex shows active DFG-in conformation distinct from wild-type
- Ki=100 pM for T315I vs 3
- 800 pM for wild-type (PMID:25686603)
- Axitinib suppressed T315I autophosphorylation and Ba/F3 cell proliferation with 10-fold higher potency than wild-type ABL1 (PMID:25686603)
Still missing
- Functional evidence is in somatic/BCR-ABL1 fusion context
- not germline ABL1 function
Sources
PM1 ModerateThe c.1001C>T (p.Thr334Ile) variant alters the gatekeeper residue (Thr315 in canonical numbering) located in the ATP-binding pocket of the ABL1 kinase domain. This is a critical functional domain of the tyrosine kinase where pathogenic missense variants cluster without benign variation. The ClinVar 3billion submission also applied PM1. Details ▾Hide ▴
Evidence considered
- Residue Thr315/Thr334 is the gatekeeper residue in the ABL1 kinase domain ATP-binding pocket
- The gatekeeper residue forms a critical hydrogen bond with STI-571 (PMID:10988075)
- Located in a well-established functional domain (protein kinase domain) without benign variation at this residue (absent from gnomAD)
- ClinVar SCV002318661 extracted PM1 as an applicable criterion
Sources
PM2 ModerateThe variant is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0 population databases (allele frequency 0.0%). Per non-VCEP generic ACMG thresholds, PM2 applies when a variant is absent or present at <0.1% in population databases. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (exomes)
- Absent from gnomAD v4.1 (exomes)
- Absent from gnomAD-Canada v1.0 (HostSeq genomes)
Sources
PP3 SupportingREVEL score of 0.587 exceeds the 0.5 threshold for deleterious prediction. BayesDel score of 0.237 provides additional in silico support. SpliceAI predicts no splicing impact (max delta 0.00), consistent with a missense variant whose pathogenic mechanism is at the protein level. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.587 (deleterious
- >0.5 threshold)
- BayesDel score: 0.236673
- SpliceAI max delta: 0.00 (no splice impact)
Sources
Not met · 12 · evaluated, threshold not reached
PP1 No cosegregation data for NM_007313.2:c.1001C>T in affected family members was identified. PP1 requires cosegregation with disease in multiple affected family members. Details ▾Hide ▴
Evidence considered
- No family cosegregation data available
Still missing
- Cosegregation data absent
PP4 PP4 requires that the patient's phenotype or family history is highly specific for a disease with a single genetic etiology. No patient phenotype information was provided for this variant in a germline disease context. Details ▾Hide ▴
Evidence considered
- No patient phenotype data available for germline assessment
Still missing
- Patient phenotype data absent from case inputs
BA1 The variant is absent from gnomAD v2.1, v4.1, and Canada. Allele frequency 0.0% is well below the BA1 threshold of >1%. Details ▾Hide ▴
Evidence considered
- Allele frequency 0.0% across all gnomAD datasets
Sources
BS1 The variant is absent from all gnomAD population databases (allele frequency 0.0%). Does not meet the BS1 threshold of >0.3%. Details ▾Hide ▴
Evidence considered
- Allele frequency 0.0% across all gnomAD datasets
Sources
BS2 The variant has not been observed in a healthy adult individual for a disorder with full penetrance expected at an early age. BS2 requires observation in trans for recessive disorders or in a healthy adult for dominant fully penetrant early-onset disorders. Details ▾Hide ▴
Evidence considered
- No observation in healthy adults identified
BS3 Well-established in vitro functional studies (PMID:11423618, PMID:25686603) demonstrate a damaging effect of the T315I substitution on ABL1 kinase drug binding, not a benign effect. BS3 requires functional studies showing no damaging effect. Details ▾Hide ▴
Evidence considered
- Functional studies demonstrate damaging effect (drug resistance)
- opposite direction from BS3
Sources
BS4 No segregation data demonstrating lack of cosegregation with disease in affected family members. BS4 requires such evidence to be met. Details ▾Hide ▴
Evidence considered
- No segregation data available
BP1 BP1 applies when a missense variant occurs in a gene for which primarily truncating variants are known to cause disease. ABL1-associated germline disorders (CHDSKM, HADS) are caused by both missense (gain-of-function: p.Tyr245Cys, etc.) and loss-of-function variants. BP1 is not met. Details ▾Hide ▴
Evidence considered
- ABL1 germline disease involves both missense (CHDSKM) and loss-of-function (HADS) variants
BP2 No observation of NM_007313.2:c.1001C>T in trans with a pathogenic variant for a fully penetrant dominant disorder, or in cis with a pathogenic variant in any inheritance pattern. Details ▾Hide ▴
Evidence considered
- No trans or cis observations identified
BP4 REVEL score of 0.587 predicts a deleterious effect (>0.5 threshold). BP4 requires multiple lines of computational evidence suggesting no impact on gene or gene product, which is contradicted by the REVEL prediction. SpliceAI max delta of 0.00 alone is insufficient to override the REVEL prediction. Details ▾Hide ▴
Evidence considered
- REVEL 0.587 (deleterious) contradicts BP4
- SpliceAI max delta 0.00 (no splicing impact)
Sources
revelspliceai ↗
BP5 BP5 requires the variant to be found in a case with an alternate molecular basis for disease. No such observation was identified. Details ▾Hide ▴
Evidence considered
- No alternate molecular basis observation identified
BP6 ClinVar classifies this variant as Likely pathogenic (criteria provided, single submitter) and Pathogenic (OMIM, no assertion criteria). BP6 requires a reputable source to report the variant as benign. ClinVar reports are in the opposite direction. Details ▾Hide ▴
Evidence considered
- ClinVar classification is Likely pathogenic
- no reputable benign classification exists
Sources
Not assessed · 6 · no assessment recorded
PS2 No de novo germline observation of NM_007313.2:c.1001C>T was identified in the reviewed literature. The variant is predominantly reported in somatic/acquired contexts (leukemia drug resistance). Details ▾Hide ▴
Evidence considered
- No germline de novo report found
Still missing
- Germline de novo occurrence data unavailable
PS4 The variant has been observed in 6 of 9 relapsed CML patients (PMID:11423618) and is reported 91 times in COSMIC (COSV59323790), but all observations are in somatic/acquired leukemia contexts. No germline case-control data comparing affected individuals to population controls is available for this variant. Details ▾Hide ▴
Evidence considered
- 6/9 relapsed CML patients harbor T315I (PMID:11423618)
- COSMIC n=91 somatic entries
Still missing
- No germline case-control prevalence data
- somatic observations cannot be directly applied to germline PS4
Sources
PM6 No assumed or confirmed de novo occurrence of NM_007313.2:c.1001C>T was identified in the reviewed literature in a germline context. PM6 requires assumed de novo with unconfirmed maternity/paternity. Details ▾Hide ▴
Evidence considered
- No germline de novo report identified
Still missing
- Germline de novo data unavailable
PP2 PP2 requires a missense variant in a gene with a low rate of benign missense variation and where missense variants are a common disease mechanism. GnomAD missense constraint (Z-score) data was not retrieved for ABL1, and no HCI prior score is available. Cannot formally assess PP2 without gene-level missense constraint metrics. Details ▾Hide ▴
Evidence considered
- HCI prior not found for ABL1
- no gnomAD missense Z-score available
Still missing
- GnomAD missense constraint data not retrieved
PP5 ClinVar variation 12624 is classified as Likely pathogenic by a single submitter with criteria provided (3billion) and as Pathogenic by OMIM (no assertion criteria). The pediatric CML guideline (PMID:24976289) lists T315I among known resistance mutations but provides no independent variant-level evidence. This does not meet the PP5 threshold requiring a reputable source to have recently reported the variant as pathogenic with evidence not independently available to the laboratory. Details ▾Hide ▴
Evidence considered
- ClinVar: Likely pathogenic (single submitter
- criteria provided)
- PMID:24976289: T315I listed among BCR-ABL1 resistance mutations in pediatric CML guidelines
- no variant-specific evidence
Still missing
- No multi-submitter expert consensus classification available
Sources
PS5 ClinVar lists the variant as Likely pathogenic from a single clinical testing submitter (3billion, criteria provided) and Pathogenic from OMIM (no assertion criteria). These do not meet the PS5 threshold requiring a reputable source recently reporting the variant as pathogenic with evidence not independently available. Details ▾Hide ▴
Evidence considered
- ClinVar variation 12624: Likely pathogenic (single submitter with criteria)
- Pathogenic (OMIM
- no criteria)
Still missing
- No multi-submitter expert consensus classification available
Sources
Not applicable · 4· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_007313.2:c.1001C>T is a missense variant (p.Thr334Ile). Per ClinGen SVI PVS1 recommendations (PMC6185798), it does not fall into the null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants. The generic PVS1 framework does not apply. Details ▾Hide ▴
Evidence considered
- Missense substitution
- variant_bucket=other
- apply_generic_pvs1_framework=false
Sources
PS1 N/APS1 applies when a novel nucleotide change produces the same amino acid change as a previously established pathogenic variant. NM_007313.2:c.1001C>T is itself the established pathogenic T315I gatekeeper variant, not a novel nucleotide substitution yielding the same missense change. Details ▾Hide ▴
Evidence considered
- Variant is the canonical T315I gatekeeper mutation
- no alternative nucleotide change encoding T334I identified
PM5 N/APM5 applies when a novel missense variant occurs at an amino acid residue where a different pathogenic missense change has been previously established. NM_007313.2:c.1001C>T (p.Thr334Ile/T315I) is itself the well-established pathogenic change at this residue. Per pm5_candidates.json, no eligible same-residue comparator variants satisfying classic PM5 semantics were identified. Details ▾Hide ▴
Evidence considered
- T315I is the established pathogenic variant at this residue
- PM5 candidate harvesting returned empty
BP7 N/ANM_007313.2:c.1001C>T is a missense variant (p.Thr334Ile). BP7 applies only to synonymous variants with no predicted splice impact. SpliceAI max delta is 0.00, but the variant is inherently missense and BP7 is reserved for synonymous variants. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is reserved for synonymous variants
Identifiers
- Gene
- ABL1
- Transcript
- NM_007313.2
- Coding (HGVS c.)
- NM_007313.2:c.1001C>T
- Protein (HGVS p.)
- NP_009297.2:p.(Thr334Ile)
- GRCh38
- chr9:130872896 C>T
- GRCh37
- chr9:133748283 C>T
- ClinVar
- 12624
- COSMIC
- COSV59323790
Gene diagram
Every interpreted variant in ABL1, mapped onto the exon structure of NM_007313.2. Select a row to find it on the plot.
ABL1NM_007313.2
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 ABL1
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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
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.587
- BayesDel
- 0.237
How the predictions were used
PP3 SupportingREVEL score of 0.587 exceeds the 0.5 threshold for deleterious prediction. BayesDel score of 0.237 provides additional in silico support. SpliceAI predicts no splicing impact (max delta 0.00), consistent with a missense variant whose pathogenic mechanism is at the protein level. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.587 (deleterious
- >0.5 threshold)
- BayesDel score: 0.236673
- SpliceAI max delta: 0.00 (no splice impact)
Sources
BP4 REVEL score of 0.587 predicts a deleterious effect (>0.5 threshold). BP4 requires multiple lines of computational evidence suggesting no impact on gene or gene product, which is contradicted by the REVEL prediction. SpliceAI max delta of 0.00 alone is insufficient to override the REVEL prediction. Details ▾Hide ▴
Evidence considered
- REVEL 0.587 (deleterious) contradicts BP4
- SpliceAI max delta 0.00 (no splicing impact)
Sources
revelspliceai ↗
BP7 N/ANM_007313.2:c.1001C>T is a missense variant (p.Thr334Ile). BP7 applies only to synonymous variants with no predicted splice impact. SpliceAI max delta is 0.00, but the variant is inherently missense and BP7 is reserved for synonymous variants. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is reserved for synonymous variants
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.587. BayesDel score = 0.236673.
6 paper records listed. 3 cited in the classification.
Cited in the classification
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PMID 10988075 ↗Structural mechanism for STI-571 inhibition of abelson tyrosine kinase.Schindler T et al. · 2000 Sep 15Reports the crystal structure of the wild-type ABL1 catalytic domain bound to an STI-571 variant at 2.4 Å resolution. Identifies Thr315 as a residue whose side chain forms a critical hydrogen bond with STI-571. The T315I mutation is not mentioned in this paper; the study was published prior to the clinical discovery of the T315I resistance mutation.→ PM1 Does not name this variant
Source detail
Thr315 is among those that form critical hydrogen bonds with STI-571.
Location Results, paragraph describing hydrogen bonding interactions with inhibitor
Context Crystallography of murine ABL1 kinase domain (aa 229-515) with STI-571 variant; spectrophotometric kinase assay for inhibition
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PMID 11423618 ↗Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification.Gorre ME et al. · 2001 Aug 3T315I (Thr315Ile) identified in 6 of 9 STI-571-resistant CML patients by cDNA sequencing. Reconstitution of T315I into wild-type p210 BCR-ABL in 293T cells confirmed the mutant retained phosphotyrosine activity at all STI-571 concentrations tested, demonstrating the T315I substitution is sufficient to confer drug resistance. Structural modeling predicted the isoleucine substitution would eliminate a critical hydrogen bond with STI-571 and create a steric clash.→ PS3 Names this variant
Source detail
A single, identical C→T nucleotide (nt) change was detected at ABL nt 944 in six of nine cases examined. ... This single nucleotide C→T change results in a threonine to isoleucine substitution at position 315 (Thr315→Ile; T315I) of c-Abl.
Location Abstract; Results, paragraphs 2-4; Fig. 4
Context BCR-ABL reconstitution assay, 293T cells; STI-571 dose-response (0-10 µM); anti-phosphotyrosine and anti-Abl immunoblotting
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PMID 25686603 ↗Axitinib effectively inhibits BCR-ABL1(T315I) with a distinct binding conformation.Pemovska T et al. · 2015 Mar 5BCR-ABL1(T315I) gatekeeper mutation shown to be potently inhibited by axitinib. Crystal structures of axitinib bound to ABL1(T315I) revealed an active DFG-in conformation distinct from the DFG-out conformation in wild-type ABL1. Axitinib inhibited ABL1(T315I) with Ki=100 pM versus Ki=3,800 pM for wild-type. Axitinib suppressed T315I autophosphorylation and Ba/F3 cell proliferation with ~10-fold higher potency compared to wild-type. Clinical treatment of a T315I-positive CML patient resulted in rapid reduction of T315I transcript levels.→ PS3 Names this variant
Source detail
The BCR–ABL1 kinase domain gatekeeper mutation Thr315Ile (T315I) confers resistance to all approved ABL1 inhibitors except ponatinib, which has toxicity limitations.
Location Abstract; Results, paragraphs 1-6; Fig. 2-4
Context Crystallography (axitinib-ABL1 and axitinib-ABL1(T315I) co-crystals); biochemical kinase inhibition (Ki determination); Ba/F3 cell proliferation and autophosphorylation ELISA; ex vivo drug sensitivity testing of primary CML/Ph+ ALL patient cells; clinical case treatment (5 mg axitinib twice daily)
Other recorded publications
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Richards S et al. · 2015ACMG/AMP 2015 standards and guidelines for the interpretation of sequence variants. Provides the generic framework for variant classification including the criteria definitions and combination rules used in this assessment. Does not discuss ABL1, T315I, or any specific variant.Does not name this variant
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PMID 24976289 ↗Managing children with chronic myeloid leukaemia (CML): recommendations for the management of CML in children and young people up to the age of 18 years.de la Fuente J et al. · 2014International BFM Group pediatric CML management guideline. Lists T315I among common BCR-ABL1 kinase domain mutations (M244V, G250E, Y253F/H, E255K/V, T315I, F317L, M351T) and notes that TKD mutation analysis is reserved for cases of suboptimal response or treatment failure. Provides no variant-specific clinical, functional, or prevalence data for T315I.Names this variant
Quoted passage
For the most frequent BCR-ABL1 gene mutations (i.e. M244V, G250E, Y253F/H, E255K/V, T315I, F317L, M351T, ...)
Section: Tyrosine kinase domain mutations; Table listing mutations
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PMID 36063163 ↗Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC).Horak P et al. · 2022Joint ClinGen/CGC/VICC recommendations for somatic variant oncogenicity classification. Provides standards for classifying somatic variants in cancer. Does not discuss ABL1 T315I specifically; referenced by KCCC/NGS Laboratory ClinVar submission as a methodological reference.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
1 Likely pathogenic · 1 association
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/12624/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/9-133748283-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr9-130872896-C-T?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/9-130872896-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007313.2%3Ac.1001…
- OncoKB ↗www.oncokb.org/gene/ABL1/T334I
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=140859604
- 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
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
Error retrieving ClinVar entry.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.587. BayesDel score = 0.236673.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. ABL1, a tyrosine kinase, is frequently altered by chromosomal translocations in leukemia.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV59323790, n = 91 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.