0%
EGFRc.2317_2319dupLikely pathogenic
Print report
Variant interpretation report

EGFR c.2317_2319dup, p.(His773dup)

NM_005228.4:c.2317_2319dup NP_005219.2:p.(His773dup) View identifiers
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.

About EGFR

No gene-level summary was recorded for this case.

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: 3 Benign evidence criteria: 0
Pathogenic criteria applied · 3
PM1Moderate
PM1 · moderate

p.His773dup is located in the EGFR tyrosine kinase domain, specifically in exon 20 within the C-helix/post-C-helix region (residues 762–823). This is a well-characterized critical functional domain essential for kinase activity and ATP/drug binding. Exon 20 insertions in this region are established oncogenic drivers in NSCLC.

PM2Moderate
PM2 · moderate

NM_005228.4:c.2317_2319dupCAC is absent from all population databases: gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0. Under generic ACMG/AMP non-VCEP rules, absence from population databases meets PM2 at moderate strength (AF < 0.1%).

PM4Moderate
PM4 · moderate

NM_005228.4:c.2317_2319dupCAC causes an in-frame duplication (p.His773dup), resulting in a protein length change by insertion of one amino acid in a non-repeat region of EGFR. PM4 applies to in-frame deletions/insertions in non-repeat regions.

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: PM1 moderate, PM2 moderate, PM4 moderate; combination = 3 moderate, 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.

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 Uncertain significance. 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: Likely Oncogenic.

No listed criterion applied OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
15 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV51781591, n = 15 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only
COSMIC ↗Cancer Hotspots ↗
For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

28 criteria with recorded statuses: 3 met · 12 not met · 5 not assessed · 8 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM4PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

NM_005228.4:c.2317_2319dupCAC (p.His773dup) is an in-frame duplication in exon 20 of EGFR, located in the tyrosine kinase domain C-helix/post-C-helix region, a critical functional domain (PM1).

This variant is absent from all population databases including gnomAD v2.1, v4.1, and gnomAD-Canada (PM2).

The in-frame duplication results in a protein length change (p.His773dup) in a non-repeat region of EGFR (PM4).

ClinVar classifies this variant as Uncertain significance (Variation ID 45261, 0-star review status) based on a single clinical laboratory submission with no assertion criteria provided.

OncoKB annotates this variant as Likely Oncogenic with gain-of-function biological effect. COSMIC reports 15 somatic observations (COSV51781591), consistent with a role in tumorigenesis.

No variant-specific functional studies were identified for p.His773dup in the reviewed literature. Sister exon 20 insertion variants at His773 (His773_Val774insHis) have been characterized as conferring EGFR TKI resistance in vitro, but the exact variant has not been experimentally tested.

SpliceAI predicts no splice alteration (max delta = 0.00). REVEL and BayesDel are not applicable to this variant type.

Met · 3

PM1 Moderatep.His773dup is located in the EGFR tyrosine kinase domain, specifically in exon 20 within the C-helix/post-C-helix region (residues 762–823). This is a well-characterized critical functional domain essential for kinase activity and ATP/drug binding. Exon 20 insertions in this region are established oncogenic drivers in NSCLC. Details ▾Hide ▴
Evidence considered
  • PMID:21764376 (Yasuda 2012): Comprehensive review establishing the C-helix and post-C-helix region of exon 20 as critical for EGFR kinase domain active/inactive conformational control.
  • PMID:18676761 (Wu 2008): Documents exon 20 mutations in the tyrosine kinase domain as functionally significant.
  • OncoKB: Gain-of-function / Likely Oncogenic annotation consistent with location in critical functional domain.
Sources
PMID:21764376 ↗PMID:18676761 ↗oncokb ↗
PM2 ModerateNM_005228.4:c.2317_2319dupCAC is absent from all population databases: gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0. Under generic ACMG/AMP non-VCEP rules, absence from population databases meets PM2 at moderate strength (AF < 0.1%). Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: absent (AC=null
  • AN=null
  • AF=null)
  • gnomAD v4.1: absent (AC=null
  • gnomAD-Canada v1.0: absent (AC=0
  • AN=0
  • AF=0.0)
Sources
gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗
PM4 ModerateNM_005228.4:c.2317_2319dupCAC causes an in-frame duplication (p.His773dup), resulting in a protein length change by insertion of one amino acid in a non-repeat region of EGFR. PM4 applies to in-frame deletions/insertions in non-repeat regions. Details ▾Hide ▴
Evidence considered
  • In-frame duplication of CAC at c.2317_2319
  • predicting p.His773dup.
  • EGFR does not contain repetitive regions at this position.

Not met · 12 · evaluated, threshold not reached

PS2 No de novo observation has been reported for NM_005228.4:c.2317_2319dupCAC (p.His773dup). None of the reviewed publications describe a de novo germline event for this variant. Details ▾Hide ▴
Evidence considered
  • No de novo data found in the case materials.
Still missing
  • No de novo testing or family studies available.
PS3 No direct functional data exists for p.His773dup specifically. EGFR exon 20 insertions at nearby residues (His773_Val774insHis, Pro772_His773insAsn) have been characterized in vitro as conferring TKI resistance and gain-of-function, but the exact variant has not been experimentally tested. Variant-specific functional evidence is required for PS3; domain-level inference from sparse testing of sister variants does not satisfy PS3 thresholds. Details ▾Hide ▴
Evidence considered
  • PMID:21764376 (Yasuda 2012): His773_Val774insHis tested in Ba/F3 and NIH-3T3 cells
  • IC50 >3 µM for gefitinib/erlotinib
  • confirming TKI resistance. His773dup not tested.
  • PMID:18676761 (Wu 2008): H773_V774insH noted as exon 20 insertion conferring poor gefitinib response. His773dup not mentioned.
  • OncoKB classifies variant as Likely Oncogenic / Gain-of-function
  • but this is a curated label
  • not direct experimental data for the variant.
Still missing
  • No variant-specific functional assay for p.His773dup.
Sources
PMID:21764376 ↗PMID:18676761 ↗
PS4 No case-control data or statistically enriched observation of NM_005228.4:c.2317_2319dupCAC in affected individuals versus controls. COSMIC reports 15 somatic observations, but this represents somatic tumor profiling, not germline case-control data suitable for PS4. Details ▾Hide ▴
Evidence considered
  • COSMIC: 15 somatic observations (COSV51781591)
  • no germline case-control data.
Still missing
  • No germline case-control or cohort enrichment data.
PM6 No de novo observation has been reported for NM_005228.4:c.2317_2319dupCAC in any of the reviewed publications. PM6 requires confirmed de novo status. Details ▾Hide ▴
Evidence considered
  • No de novo data found.
Still missing
  • No de novo testing data available.
PP1 No cosegregation data is available for NM_005228.4:c.2317_2319dupCAC. PP1 requires evidence of segregation with disease in affected family members. Details ▾Hide ▴
Evidence considered
  • No family studies or segregation data available.
Still missing
  • No segregation data.
PP3 In silico predictors provide no evidence supporting pathogenicity. SpliceAI max delta score is 0.00 (no splice impact). REVEL and BayesDel scores are unavailable (not a single nucleotide substitution). HCI prior is not available for EGFR. No computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
  • SpliceAI: max delta = 0.00 (no predicted splice alteration).
  • REVEL/BayesDel: not applicable (non-SNV variant).
  • HCI prior: not found for EGFR.
Still missing
  • No in silico scores applicable to in-frame duplication variants.
Sources
spliceai ↗
PP5 ClinVar classifies this variant as Uncertain significance (Variation ID 45261) with review status 'no assertion criteria provided' (0 stars) by a single clinical laboratory. PP5 requires a reputable source (≥3-star expert panel) to have classified the variant as pathogenic. This 0-star VUS classification does not meet PP5 threshold. Details ▾Hide ▴
Evidence considered
  • ClinVar Variation ID 45261: 1 submitter (LMM
  • Mass General Brigham)
  • classification: Uncertain significance
  • review status: no assertion criteria provided (0 stars).
Sources
clinvar ↗
BA1 The variant is absent from all population databases (gnomAD v2.1, v4.1, Canada). BA1 requires an allele frequency >1% in population databases. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: absent
  • gnomAD v4.1: absent
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS1 The variant is absent from all population databases. BS1 requires an allele frequency >0.3% under generic ACMG non-VCEP rules. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: absent
  • gnomAD v4.1: absent
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS3 Available evidence suggests gain-of-function, not benign effect. OncoKB classifies this variant as Likely Oncogenic with gain-of-function biological effect. Sister exon 20 insertion variants at His773 (His773_Val774insHis) have been shown to confer TKI resistance in vitro. No functional data support a benign or neutral effect for this variant or its region. Details ▾Hide ▴
Evidence considered
  • OncoKB: Likely Oncogenic
  • Gain-of-function.
  • PMID:21764376: His773_Val774insHis tested in Ba/F3 and NIH-3T3
  • IC50 >3 µM for gefitinib/erlotinib.
Sources
oncokb ↗PMID:21764376 ↗
BP4 No in silico evidence supports a benign effect. SpliceAI predicts no splice alteration (delta = 0.00), which is neutral but not positively benign. REVEL/BayesDel are not applicable to duplication variants. No multiple lines of computational evidence suggest no impact. Details ▾Hide ▴
Evidence considered
  • SpliceAI: max delta = 0.00 (no splice alteration — neutral
  • not benign).
  • REVEL/BayesDel not applicable.
Still missing
  • No in silico tools validated for in-frame duplication variants.
Sources
spliceai ↗
BP6 ClinVar classifies this variant as Uncertain significance (Variation ID 45261) with review status 'no assertion criteria provided' (0 stars). BP6 requires a reputable source (≥3-star expert panel) to have classified the variant as benign. Details ▾Hide ▴
Evidence considered
  • ClinVar Variation ID 45261: 1 submitter
  • classification: Uncertain significance
  • review status: no assertion criteria provided (0 stars).
Sources
clinvar ↗

Not assessed · 5 · no assessment recorded

PP4 No patient phenotype information is available to evaluate specificity of the patient's clinical presentation for EGFR-related disease. Details ▾Hide ▴
Evidence considered
  • No phenotype data provided.
Still missing
  • Patient phenotype not available for PP4 evaluation.
BS2 No data on observation of this variant in healthy adult controls (homozygous or heterozygous) is available. Details ▾Hide ▴
Evidence considered
  • No healthy control data available.
Still missing
  • No observation data in healthy controls.
BS4 No segregation data is available to evaluate lack of cosegregation with disease. Details ▾Hide ▴
Evidence considered
  • No family or segregation data available.
Still missing
  • No segregation data.
BP2 No data available on whether this variant has been observed in trans with a known pathogenic variant in EGFR. Details ▾Hide ▴
Evidence considered
  • No trans-configuration data available.
Still missing
  • No data on observation in trans with pathogenic variant.
BP5 No data available on whether an alternate molecular basis for disease has been identified in the proband. Details ▾Hide ▴
Evidence considered
  • No alternate molecular cause data available.
Still missing
  • No data on alternate molecular cause.
Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_005228.4:c.2317_2319dup is an in-frame duplication (p.His773dup), not a null variant (nonsense, frameshift, or canonical ±1,2 splice consensus). The generic PVS1 framework explicitly excludes this variant bucket. Details ▾Hide ▴
Evidence considered
  • In-frame duplication
  • does not fall into PVS1 null-variant buckets per PMC6185798.
Sources
pvs1_generic_framework ↗
PS1 N/APS1 applies to a nucleotide change producing the same amino acid change as a previously established pathogenic missense variant. This variant is an in-frame duplication (p.His773dup), not a missense substitution. Details ▾Hide ▴
Evidence considered
  • In-frame duplication variant type is outside PS1 scope.
PM5 N/APM5 applies to a different missense change at the same codon as an established pathogenic variant. This variant is an in-frame duplication (p.His773dup), not a missense substitution. The PM5 candidate collector was unable to confirm classic same-residue PM5 semantics for this variant type. Details ▾Hide ▴
Evidence considered
  • Variant type (duplication) is outside PM5 scope
  • no same-residue missense comparators applicable.
Sources
pm5_candidates
PP2 N/APP2 applies to missense variants in a gene with a low rate of benign missense variation. This variant is an in-frame duplication, not a missense substitution. Details ▾Hide ▴
Evidence considered
  • In-frame duplication variant type is outside PP2 scope.
BP1 N/ABP1 applies to missense variants in genes where truncating variants are the primary disease mechanism. This variant is an in-frame duplication, not a missense substitution. Details ▾Hide ▴
Evidence considered
  • Variant type (in-frame duplication) is outside BP1 scope.
BP3 N/ABP3 applies to in-frame deletions/insertions in repetitive regions without known function. While this is an in-frame duplication, the EGFR exon 20 C-helix region is a well-characterized functional domain, not a repetitive region of unknown significance. Details ▾Hide ▴
Evidence considered
  • EGFR exon 20 tyrosine kinase domain is a critical functional domain
  • BP3 not applicable.
Sources
PMID:21764376 ↗
BP7 N/ABP7 applies to synonymous variants with no predicted splice impact. NM_005228.4:c.2317_2319dupCAC is an in-frame duplication causing p.His773dup, not a synonymous variant. Details ▾Hide ▴
Evidence considered
  • In-frame duplication
  • not synonymous.
PS5 N/APS5 is not a standard ACMG/AMP 2015 criterion and no PS5 rule definition is provided in the case materials. Details ▾Hide ▴
Evidence considered
  • No PS5 definition available.

Identifiers

Gene
EGFR
Transcript
NM_005228.4
Coding (HGVS c.)
NM_005228.4:c.2317_2319dup
Protein (HGVS p.)
NP_005219.2:p.(His773dup)
GRCh38
chr7:55181324 C>CCCA
GRCh37
chr7:55249017 C>CCCA
ClinVar
45261
COSMIC
COSV51781591

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…
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

Pangolin splice lossmagnitude shown
-0.000
Pangolin splice gain
0.000

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

PP3 In silico predictors provide no evidence supporting pathogenicity. SpliceAI max delta score is 0.00 (no splice impact). REVEL and BayesDel scores are unavailable (not a single nucleotide substitution). HCI prior is not available for EGFR. No computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
  • SpliceAI: max delta = 0.00 (no predicted splice alteration).
  • REVEL/BayesDel: not applicable (non-SNV variant).
  • HCI prior: not found for EGFR.
Still missing
  • No in silico scores applicable to in-frame duplication variants.
Sources
spliceai ↗
BP4 No in silico evidence supports a benign effect. SpliceAI predicts no splice alteration (delta = 0.00), which is neutral but not positively benign. REVEL/BayesDel are not applicable to duplication variants. No multiple lines of computational evidence suggest no impact. Details ▾Hide ▴
Evidence considered
  • SpliceAI: max delta = 0.00 (no splice alteration — neutral
  • not benign).
  • REVEL/BayesDel not applicable.
Still missing
  • No in silico tools validated for in-frame duplication variants.
Sources
spliceai ↗
BP7 N/ABP7 applies to synonymous variants with no predicted splice impact. NM_005228.4:c.2317_2319dupCAC is an in-frame duplication causing p.His773dup, not a synonymous variant. Details ▾Hide ▴
Evidence considered
  • In-frame duplication
  • not synonymous.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

8 paper records listed. 2 cited in the classification. None of the listed paper records explicitly indicates that the variant is named.

Cited in the classification

  • Lung cancer with epidermal growth factor receptor exon 20 mutations is associated with poor gefitinib treatment response.
    Reports EGFR exon 20 mutations including A767_V769dupASV, H773_V774insH, and H773R as associated with poor gefitinib response in NSCLC. NM_005228.4:c.2317_2319dupCAC (p.His773dup) was not identified; the mutations at residue 773 are distinct (H773_V774insH, H773R, P772_H773insYNP, H773Y).
    → PM1 Does not name this variant
    PMID 18676761 ↗
    Source detail
    Mutations in exon 20 could be in-frame duplication and/or insertion, such as A767_V769dupASV or H773_V774insH. They could also be point mutations. Examples of reported exon 20 mutations in literature are V765M, S768I, H773R, and T790M.

    Location Table 1, Table 2; introduction (line 42-44)

    Context DNA sequencing of NSCLC tumor specimens; clinical cohort (n=23 with exon 20 mutations)

  • EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications.
    Comprehensive review of EGFR exon 20 insertion mutations in NSCLC. Catalogs 122 exon 20 insertions including His773_Val774insHis, His773_Val774dupHisVal, and Pro772_His773insAsn. NM_005228.4:c.2317_2319dupCAC (p.His773dup, a single amino acid duplication) is NOT listed in the compiled mutation table. His773_Val774insHis was tested in vitro and shown resistant to gefitinib/erlotinib (IC50 >3 µM).
    → PM1 Does not name this variant
    PMID 21764376 ↗
    Source detail
    His773_Val774insHis,27 have been shown to be resistant to gefitinib and erlotinib; the insertions had 50% inhibitory concentrations (IC50) to gefitinib or erlotinib, of higher than 3 μmol/L.

    Location Table 1 (EGFR exon 20 insertion mutations by amino acid position); Preclinical Studies section

    Context Review; functional data from Ba/F3 and NIH-3T3 surrogate assays for His773_Val774insHis

Other recorded publications

  • Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small cell lung cancer.
    Reports EGFR tyrosine kinase domain mutations (exons 18-21) as predictive/prognostic for gefitinib response in NSCLC. Describes deletions in exon 19, substitution mutations including L858R, and notes no duplication/insertion mutations were found in exon 20 in this cohort. NM_005228.4:c.2317_2319dupCAC (p.His773dup) was not identified.
    Does not name this variant
    PMID 15897572 ↗
    Quoted passage
    We identified one deletion mutation and four substitution mutations but no duplication/insertion mutations in exon 20.

    Results: EGFR mutations section; Table 2; Discussion

  • EGFR exon 20 insertion mutation in Japanese lung cancer.
    Reports EGFR exon 20 insertion mutations in Japanese NSCLC patients. Describes various exon 20 insertion mutations but NM_005228.4:c.2317_2319dupCAC (p.His773dup) was not identified.
    Does not name this variant
    PMID 17686547 ↗
  • Second-line treatments after first-line gefitinib therapy in advanced nonsmall cell lung cancer.
    Discusses second-line treatment after first-line gefitinib in advanced NSCLC. Mentions H773Y and P772_H773insYNP in one patient. NM_005228.4:c.2317_2319dupCAC (p.His773dup) was not identified.
    Does not name this variant
    PMID 19536777 ↗
  • The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma.
    Wu G et al. · 2014
    Genomic landscape study of 127 pediatric HGGs (DIPG and NBS-HGG). Reports recurrent mutations in ACVR1, TP53, H3F3A, and other genes. NM_005228.4:c.2317_2319dupCAC (p.His773dup) was not identified in this study.
    Does not name this variant
    PMID 24705251 ↗
  • Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.
    Mackay A et al. · 2017
    Integrated meta-analysis of >1,000 pediatric HGGs and DIPGs. Reports co-segregating mutations in histone-mutant subgroups. NM_005228.4:c.2317_2319dupCAC (p.His773dup) was not identified.
    Does not name this variant
    PMID 28966033 ↗
  • Pediatric bithalamic gliomas have a distinct epigenetic signature and frequent EGFR exon 20 insertions resulting in potential sensitivity to targeted kinase inhibition.
    Mondal G et al. · 2020
    Reports frequent EGFR exon 20 insertion mutations in pediatric bithalamic gliomas with distinct epigenetic signatures. NM_005228.4:c.2317_2319dupCAC (p.His773dup) was not identified in this study.
    Does not name this variant
    PMID 32303840 ↗

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 Uncertain significance 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

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 Uncertain significance (1 clinical laboratory). (ClinVarID = 45261)

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: Gain-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; COSV51781591, n = 15 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.