About EGFR
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
EGFR c.2237_2255delinsT, p.(Glu746_Ser752delinsVal)
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
The exact variant (p.E746_S752delinsV) has been directly observed and characterized in a clinical-functional context. In Han et al. 2005 (PMID:15710947), a patient harboring this specific EGFR exon 19 deletion demonstrated a partial response to gefitinib with prolonged time to progression (22+ months) and overall survival (22+ months), consistent with an activating EGFR kinase domain mutation. Additional in vitro functional characterization of related exon 19 deletions (del L747-S752) by Pao et al. 2004 (PMID:15329413) demonstrated altered EGFR phosphorylation and increased sensitivity to tyrosine kinase inhibitors, confirming gain-of-function for this class of deletion. OncoKB classifies the variant as Oncogenic with gain-of-function effect, and the variant is recurrently observed in somatic cancers (COSMIC, n=87).
PM1Moderate
PM1 · moderate
The variant deletes amino acids 746-752 within the EGFR tyrosine kinase domain, a well-characterized critical functional domain. This region encompasses the ATP-binding pocket and is a recognized hotspot for activating oncogenic mutations in non-small-cell lung cancer. In-frame deletions in this region (exon 19, codons 746-759) are recurrently described as gain-of-function alterations in the literature. The variant removes the conserved LREA motif (codons 747-750), known to be critical for kinase regulation.
PM2Supporting
PM2 · supporting
The variant is absent from all population databases including gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0, consistent with a rare variant not observed in the general population (allele frequency <0.1%).
PM4Moderate
PM4 · moderate
The variant is an in-frame deletion of 7 amino acids (E746-S752) with insertion of a single valine residue within the EGFR kinase domain. This protein length change occurs in a non-repeat region and removes critical residues of the ATP-binding pocket. In-frame deletions in non-repeat regions are recognized as likely disruptive to protein structure and function per ACMG guidelines.
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 supporting, PM4 moderate; 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
0.130 maximum delta
Recorded SpliceAI maximum delta score: 0.130. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
2 reported laboratory submissions
1 drug response · 1 Likely pathogenic. 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; biological-effect context: Gain-of-function; curated oncogenicity label: Oncogenic.
COSMIC
Cancer Hotspots
Somatic evidence
87 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV51765862, n = 87 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
29 criteria with recorded statuses: 4 met · 7 not met · 9 not assessed · 9 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The variant NM_005228.4:c.2237_2255delinsT (p.E746_S752delinsV) is an in-frame deletion-insertion in exon 19 of the EGFR tyrosine kinase domain, removing amino acids 746-752 and inserting a valine residue, which eliminates the conserved LREA motif critical for kinase autoinhibition.
Functional evidence demonstrates this variant causes gain-of-function EGFR kinase activation: the exact variant (del E746-S752insV) was associated with clinical gefitinib response in a lung adenocarcinoma patient (PMID:15710947), and related exon 19 deletions were shown in vitro to alter EGFR phosphorylation and confer TKI sensitivity (PMID:15329413). OncoKB classifies the variant as Oncogenic with gain-of-function effect.
The variant is located in the EGFR tyrosine kinase domain, a well-characterized critical functional domain that is a recurrent hotspot for activating mutations in NSCLC. The deletion removes the conserved LREA motif at codons 747-750 within the ATP-binding pocket.
The variant is absent from all population databases including gnomAD v2.1, v4.1, and gnomAD-Canada v1.0, consistent with a rare variant not tolerated in the general population.
This in-frame deletion of 7 amino acids with insertion of a valine in a non-repeat, critical functional domain constitutes a significant protein length alteration expected to disrupt domain architecture.
The variant has been repeatedly observed as a somatic driver in lung adenocarcinoma (COSMIC, n=87) and is recognized in the curated OncoKB database as oncogenic, underscoring its established functional significance in cancer biology.
Met criteria: PS3 (moderate), PM1 (moderate), PM4 (moderate), PM2 (supporting). Three moderate and one supporting criterion meet the generic ACMG/AMP 2015 threshold for Likely Pathogenic classification.
No criteria match.
Met · 4
PS3 ModerateThe exact variant (p.E746_S752delinsV) has been directly observed and characterized in a clinical-functional context. In Han et al. 2005 (PMID:15710947), a patient harboring this specific EGFR exon 19 deletion demonstrated a partial response to gefitinib with prolonged time to progression (22+ months) and overall survival (22+ months), consistent with an activating EGFR kinase domain mutation. Additional in vitro functional characterization of related exon 19 deletions (del L747-S752) by Pao et al. 2004 (PMID:15329413) demonstrated altered EGFR phosphorylation and increased sensitivity to tyrosine kinase inhibitors, confirming gain-of-function for this class of deletion. OncoKB classifies the variant as Oncogenic with gain-of-function effect, and the variant is recurrently observed in somatic cancers (COSMIC, n=87). Details ▾Hide ▴
Evidence considered
- Exact variant (del E746-S752insV) identified in Han et al. 2005 Table 3
- Patient 1 with clinical gefitinib response
- In vitro functional characterization of related exon 19 deletions in Pao et al. 2004 confirming gain-of-function kinase activation
- OncoKB oncogenic classification with gain-of-function context
- Recurrent in somatic cancers (COSMIC
- n=87)
Still missing
- Functional data is from somatic/lung cancer context rather than germline
- direct in vitro characterization of the exact E746_S752delinsV construct was not performed in isolation
Sources
PM1 ModerateThe variant deletes amino acids 746-752 within the EGFR tyrosine kinase domain, a well-characterized critical functional domain. This region encompasses the ATP-binding pocket and is a recognized hotspot for activating oncogenic mutations in non-small-cell lung cancer. In-frame deletions in this region (exon 19, codons 746-759) are recurrently described as gain-of-function alterations in the literature. The variant removes the conserved LREA motif (codons 747-750), known to be critical for kinase regulation. Details ▾Hide ▴
Evidence considered
- Variant lies within EGFR tyrosine kinase domain (exon 19
- codons 746-752)
- Removes conserved LREA motif critical for kinase regulation (Pao et al. 2004
- Lynch et al. 2004)
- Well-established hotspot region for activating EGFR mutations in NSCLC
Sources
PM2 SupportingThe variant is absent from all population databases including gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0, consistent with a rare variant not observed in the general population (allele frequency <0.1%). Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- Absent from gnomAD-Canada v1.0
Sources
PM4 ModerateThe variant is an in-frame deletion of 7 amino acids (E746-S752) with insertion of a single valine residue within the EGFR kinase domain. This protein length change occurs in a non-repeat region and removes critical residues of the ATP-binding pocket. In-frame deletions in non-repeat regions are recognized as likely disruptive to protein structure and function per ACMG guidelines. Details ▾Hide ▴
Evidence considered
- In-frame deletion of codons 746-752 with valine insertion
- Non-repeat region in the EGFR tyrosine kinase domain
- Removes conserved LREA motif controlling kinase autoinhibition
Sources
Not met · 7 · evaluated, threshold not reached
PP5 ClinVar classification for this variant (Variation ID 177652) is 'drug response' with review status 'no assertion criteria provided'. This does not constitute a reputable source reporting the variant as pathogenic. The ClinVar review status is 0 stars, which does not meet the PP5 threshold of 3-star expert panel classification. The ClinVar-submitted PMIDs (15118073, 15118125) do not contain the exact variant. None of the guideline papers cataloged under PP5 criteria index (PMID:23619274, 24627688, 29355391, 29398453, 34131312) were found to specifically reference NM_005228.4:c.2237_2255delinsT. Details ▾Hide ▴
Evidence considered
- ClinVar classification: drug response (0 stars
- no assertion criteria)
- No 3-star expert panel classification available
Sources
BA1 The variant is absent from all population databases (gnomAD v2.1, v4.1, gnomAD-Canada). Allele frequency does not exceed the 1% BA1 threshold. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1
- v4.1
- and gnomAD-Canada
Sources
BS1 The variant is absent from all population databases. Allele frequency does not exceed the 0.3% BS1 threshold. Details ▾Hide ▴
Evidence considered
- Absent from all population databases
Sources
BS3 Functional studies demonstrate that this variant (and related EGFR exon 19 deletions) results in gain-of-function kinase activation, not loss of function. The variant is classified as Oncogenic with gain-of-function effect by OncoKB. In vitro data from Pao et al. 2004 (PMID:15329413) show exon 19 deletions alter EGFR phosphorylation and increase sensitivity to tyrosine kinase inhibitors, confirming a functional impact on the protein. The functional evidence does not show a benign or neutral effect. Details ▾Hide ▴
Evidence considered
- Gain-of-function oncogenic effect demonstrated in vitro and clinically
- OncoKB classification: Oncogenic
- Gain-of-function
- No evidence of neutral or benign functional effect
Sources
BP3 The variant is an in-frame deletion-insertion in the EGFR tyrosine kinase domain, which is a well-characterized functional domain, not a repetitive region without known function. BP3 requires in-frame deletions to occur in repetitive regions. Details ▾Hide ▴
Evidence considered
- Deletion occurs in critical kinase domain
- not a repetitive region
Sources
BP4 While SpliceAI predicts no significant splice impact (max delta 0.13), multiple lines of functional and clinical evidence demonstrate this variant has a gain-of-function effect on EGFR kinase activity. The computed splicing neutrality does not outweigh the established functional impact of this in-frame deletion on protein function. Details ▾Hide ▴
Evidence considered
- SpliceAI predicts no splicing impact
- Functional evidence demonstrates gain-of-function kinase activation
Sources
BP6 ClinVar classification is 'drug response' (0 stars, no assertion criteria), not 'benign' or 'likely benign'. The ClinVar review status does not meet the 3-star expert panel threshold for BP6 application. Details ▾Hide ▴
Not assessed · 9 · no assessment recorded
PS2 No data available regarding de novo occurrence with confirmed maternity and paternity. Details ▾Hide ▴
Still missing
- No parental testing data available for de novo assessment
PS4 No germline case-control or cohort data available. The variant is well-documented in somatic lung cancer (COSMIC, n=87) but this does not satisfy PS4 requirements for germline variant interpretation. Details ▾Hide ▴
Still missing
- No germline disease cohort data
- all prevalence data is from somatic tumor context
PM6 No data available regarding de novo occurrence. No parental testing reported in the reviewed literature. Details ▾Hide ▴
Still missing
- No de novo testing data available
PP1 No co-segregation data available. No family studies were identified in the literature review. Details ▾Hide ▴
Still missing
- No family co-segregation data
PP4 No patient phenotype or family history data available. Germline clinical context is not provided in the case materials. Details ▾Hide ▴
Still missing
- No proband phenotype or family history provided
BS2 No data on observation in healthy adult controls for a fully penetrant disorder. The variant is a well-known somatic oncogenic driver; germline control data are not available. Details ▾Hide ▴
Still missing
- No germline healthy control data available
BS4 No segregation data available. No family studies identified for this variant. Details ▾Hide ▴
Still missing
- No family segregation data
BP2 No data available regarding observation in trans with a pathogenic variant. Details ▾Hide ▴
Still missing
- No data on trans configuration with pathogenic variants
BP5 No data available regarding an alternate molecular basis for disease in a case harboring this variant. Details ▾Hide ▴
Still missing
- No alternate molecular basis data
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AVariant is an in-frame deletion-insertion (c.2237_2255delinsT, p.E746_S752delinsV) within the EGFR tyrosine kinase domain, not a nonsense, frameshift, or canonical ±1,2 splice consensus variant. Does not qualify for default PVS1 null-variant buckets per ClinGen SVI PVS1 recommendations (PMC6185798). Details ▾Hide ▴
Evidence considered
- In-frame indel in exon 19 kinase domain
- not a predicted null variant
Sources
PS1 N/AVariant is an in-frame deletion-insertion, not a missense change. PS1 classically applies to novel missense variants at the same codon as an established pathogenic missense variant. Not applicable to indel variants. Details ▾Hide ▴
No further detail was recorded.
PM3 N/ASkipped per instruction. Details ▾Hide ▴
No further detail was recorded.
PM5 N/AThis is an in-frame deletion-insertion, not a missense variant. The automated PM5 candidate harvesting was unable to confirm classic same-residue missense semantics. PM5 is designed for novel missense changes at the same codon as a known pathogenic missense variant. Details ▾Hide ▴
No further detail was recorded.
PP2 N/APP2 is specific to missense variants in genes with low rates of benign missense variation. This variant is an in-frame deletion-insertion, not a missense change. Details ▾Hide ▴
No further detail was recorded.
PP3 N/AIn silico predictors (REVEL, BayesDel) are designed for single-nucleotide missense variants and are not applicable to this in-frame deletion-insertion. SpliceAI predicts no significant splice impact (max delta score 0.13). No applicable computational evidence is available for this variant type. Details ▾Hide ▴
BP1 N/ABP1 is specific to missense variants in genes where primarily truncating variants cause disease. This is an in-frame deletion-insertion, not a missense variant. Details ▾Hide ▴
No further detail was recorded.
BP7 N/AVariant is an in-frame deletion-insertion altering the protein sequence, not a silent/synonymous variant with no predicted impact on splicing. Details ▾Hide ▴
No further detail was recorded.
PS5 N/AVariant is an in-frame deletion-insertion, not a single-nucleotide substitution. PS5 requires a different nucleotide change at the same position producing a different amino acid change, which is not applicable to multi-nucleotide indels. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- EGFR
- Transcript
- NM_005228.4
- Coding (HGVS c.)
- NM_005228.4:c.2237_2255delinsT
- Protein (HGVS p.)
- NP_005219.2:p.(Glu746_Ser752delinsVal)
- GRCh38
- chr7:55174774 AATTAAGAGAAGCAACATC>T
- GRCh37
- chr7:55242467 AATTAAGAGAAGCAACATC>T
- ClinVar
- 177652
- COSMIC
- COSV51765862
Gene diagram
Every interpreted variant in EGFR, mapped onto the exon structure of NM_005228.4. Select a row to find it on the plot.
EGFRNM_005228.4
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in EGFR
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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
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 While SpliceAI predicts no significant splice impact (max delta 0.13), multiple lines of functional and clinical evidence demonstrate this variant has a gain-of-function effect on EGFR kinase activity. The computed splicing neutrality does not outweigh the established functional impact of this in-frame deletion on protein function. Details ▾Hide ▴
Evidence considered
- SpliceAI predicts no splicing impact
- Functional evidence demonstrates gain-of-function kinase activation
Sources
PP3 N/AIn silico predictors (REVEL, BayesDel) are designed for single-nucleotide missense variants and are not applicable to this in-frame deletion-insertion. SpliceAI predicts no significant splice impact (max delta score 0.13). No applicable computational evidence is available for this variant type. Details ▾Hide ▴
BP7 N/AVariant is an in-frame deletion-insertion altering the protein sequence, not a silent/synonymous variant with no predicted impact on splicing. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.13).
6 paper records listed. 4 cited in the classification.
Cited in the classification
-
PMID 15118073 ↗Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.Lynch TJ et al. · 2004 May 20Identified somatic EGFR mutations in gefitinib-responsive NSCLC, including in-frame deletions in exon 19 (delE746-A750, delL747-T751insS, delL747-P753insS) and missense mutations (L858R, G719C, L861Q). Demonstrated enhanced tyrosine kinase activity in vitro for mutant EGFR. The specific c.2237_2255delinsT (p.E746_S752delinsV) was not among the variants described.→ PM1 Does not name this variant
Source detail
Four tumors had in-frame deletions, removing amino acids 746 through 750 (delE746-A750) in Patient 1, 747 through 751 (delL747-T751insS) in Patient 2, and 747 through 753 (delL747-P753insS) in Patients 3 and 4.
Location Table 2 and Results section; all listed exon 19 deletions are delE746-A750, delL747-T751insS, and delL747-P753insS
Context In vitro EGFR autophosphorylation assay in Cos-7 cells with delL747-P753insS and L858R mutant constructs
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PMID 15118125 ↗EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.Paez JG et al. · 2004 Jun 4Screened receptor tyrosine kinase genes in NSCLC and identified somatic EGFR mutations in 15/58 Japanese and 1/61 US tumors, including in-frame deletions spanning codons 746-759 (Del-1 through Del-5) and point mutations (L858R, G719S). The specific c.2237_2255delinsT (p.E746_S752delinsV) was not among the individual variants enumerated.→ PM1 Does not name this variant
Source detail
Ten tumors carried one of two overlapping 15-nucleotide deletions eliminating EGFR codons 746 to 750, starting at nucleotide 2235 or 2236 (Del-1).
Location Results section describing deletions in codons 746-759; Table S2 lists specific variants
Context Gefitinib sensitivity assay in H3255 cell line (L858R mutant), not directly testing exon 19 deletions
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PMID 15329413 ↗EGF receptor gene mutations are common in lung cancers from "never smokers" andCharacterized EGFR TK domain mutations in gefitinib- and erlotinib-sensitive NSCLC. Identified multiple exon 19 deletions including del E746-A750, del L747-S752, del E746-T751insI, and del L747-S752insQ. Provided in vitro functional characterization of the del L747-S752 mutant showing altered EGFR phosphorylation and TKI sensitivity. The exact p.E746_S752delinsV variant was not among those tested, but the closely related del L747-S752 variant was functionally characterized.→ PS3 → PM1 → PM4 Does not name this variant
Source detail
the del L747-S752 mutant also induced markedly low levels of phosphotyrosine
Location Table 1 (del L747-S752 in patient G3); Results sections describing in vitro characterization of del L747-S752 mutant
Context Transient transfection in Cos-7 cells and 293T cells, EGFR phosphorylation assay with Western blot, gefitinib sensitivity testing
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PMID 15710947 ↗Predictive and prognostic impact of epidermal growth factor receptor mutation inEvaluated EGFR mutation status in 90 consecutive NSCLC patients treated with gefitinib. The exact variant NM_005228.4:c.2237_2255delinsT (p.E746_S752delinsV) was identified in Patient 1, a female never-smoker with adenocarcinoma who achieved a partial response to gefitinib with prolonged time to progression (22+ months) and overall survival (22+ months). The deletion is described as 'del 2238-2255, 2237A>T' producing 'del E746-S752insV'.→ PS3 → PM1 → PM4 Names this variant
Source detail
del 2238-2255, 2237A>T ... del E746-S752insV
Location Table 3, Patient 1; Discussion paragraph describing exon 19 deletions between E746 and P753
Context Clinical response assessment; gefitinib 250 mg daily in advanced NSCLC; EGFR mutation analysis by DNA sequencing of exons 18, 19, 21, 23
Other recorded publications
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PMID 22483783 ↗The gefitinib long-term responder (LTR)--a cancer stem-like cell story? InsightsAnalyzed molecular characteristics of German NSCLC patients with long-term response to gefitinib in the IRESSA expanded access program. Focused on EGFR mutation status, cancer stem cell markers, and EMT markers. The specific c.2237_2255delinsT (p.E746_S752delinsV) variant was not identified in the text.Does not name this variant
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PMID 23619274 ↗American College of Medical Genetics and Genomics technical standards and guidelACMG technical standards and guidelines for microarray analysis of chromosome abnormalities in neoplastic disorders. A standards document focused on microarray methodology validation and interpretation, not on specific EGFR variants. The specific c.2237_2255delinsT was not mentioned.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 0.130
Open source ↗
ClinVar
1 drug response · 1 Likely 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/177652/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/7-55242467-AATTAAGAGAAGCAACAT…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr7-55174774-AATTAAGAGAAGCAA…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/7-55174774-AATTAAGAGAAGCAACATC-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_005228.4%3Ac.2237…
- OncoKB ↗www.oncokb.org/gene/EGFR/E746_S752delinsV
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=120690191
- 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
This variant has been reported in ClinVar as drug response (1 clinical laboratory) and as Likely pathogenic (1 clinical laboratory). (ClinVarID = 177652)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.13).
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Gain-of-function; curated oncogenicity label: Oncogenic.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV51765862, n = 87 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.