BRAFc.1447A>GUncertain significance

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Variant interpretation report

BRAF c.1447A>G, p.(Lys483Glu)

NM_004333.5:c.1447A>G NP_004324.2:p.(Lys483Glu) View identifiers

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.

About BRAF

No gene-level summary was recorded for this case.

Key facts

Condition: RASopathy
Inheritance: Autosomal dominant
Evidence used: 2 supporting (pathogenic)
Expert rules: ClinGen BRAF VCEP v2.3.0
Other laboratories (ClinVar): 1 Uncertain significance
Pipeline record: 15 Jul 2026 · version 7.0.4

Evidence considered

View criteria

Applied evidence criteria

PP2 (supporting): BRAF is a gene with a low rate of benign missense variation and where missense variants are a common mechanism of disease. The RASopathy VCEP applies PP2 at supporting strength when the gene's missense z-score exceeds 3.09 in gnomAD. BRAF has a well-established high missense constraint (missense z-score significantly > 3.09), consistent with a gene where missense variation is a common disease mechanism in RASopathies.
PP3 (supporting): The VCEP applies PP3 at supporting strength for missense variants when REVEL score is at least 0.7. The REVEL score for NM_004333.5:c.1447A>G (p.Lys483Glu) is 0.973, well above the threshold, indicating a strong in silico prediction of deleterious effect. SpliceAI predicts no splicing impact (max delta = 0.00), consistent with an amino-acid-level deleterious effect.

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 ClinGen BRAF VCEP v2.3.0. 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

PP2Supporting

PP2 · supporting

BRAF is a gene with a low rate of benign missense variation and where missense variants are a common mechanism of disease. The RASopathy VCEP applies PP2 at supporting strength when the gene's missense z-score exceeds 3.09 in gnomAD. BRAF has a well-established high missense constraint (missense z-score significantly > 3.09), consistent with a gene where missense variation is a common disease mechanism in RASopathies.

PP3Supporting

PP3 · supporting

The VCEP applies PP3 at supporting strength for missense variants when REVEL score is at least 0.7. The REVEL score for NM_004333.5:c.1447A>G (p.Lys483Glu) is 0.973, well above the threshold, indicating a strong in silico prediction of deleterious effect. SpliceAI predicts no splicing impact (max delta = 0.00), consistent with an amino-acid-level deleterious effect.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Uncertain significance

ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRAF Version 2.3.0 v2.3.0 criteria-combination framework was evaluated deterministically with applied criteria: PP2 supporting, PP3 supporting; no rule matched the adjudicated criteria.

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

1 / 1,613,408 alleles

gnomAD v4.1: 1 / 1,613,408 alleles. Recorded AF 6.19806e-07. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 3.9789e-06; MAF= 0.00040%, 1/251326 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 2.89419e-05; MAF= 0.00289%, 1/34552 alleles, homozygotes = 0).

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

No listed criterion applied

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · PP3 → SpliceAI ↗

ClinVar submissions

1 reported laboratory submissions

1 Uncertain significance. 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 Gain-of-function; curated oncogenicity label: Likely Oncogenic.

No listed criterion applied OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

19 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV56236813, n = 19 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 ClinGen BRAF VCEP v2.3.0, with the data and sources behind each one.

29 criteria with recorded statuses: 2 met · 16 not met · 0 not assessed · 11 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM3 PM4 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

NM_004333.5:c.1447A>G (p.Lys483Glu) is a missense variant in BRAF, a gene where missense variants are a common mechanism of RASopathy disease. REVEL score of 0.973 strongly predicts a deleterious effect on protein function, satisfying PP3 at supporting strength. The gene's missense z-score exceeds 3.09 in gnomAD, meeting PP2 at supporting strength. The variant is present at extremely low frequency in gnomAD (1/251,326 alleles in v2.1; 1/1,613,408 alleles in v4.1) but is not absent, so PM2 (supporting) is not met under the VCEP requirement for complete absence. The variant lies outside VCEP-defined functional domains (P-loop AA 459-474, CR3 AA 594-627) and no pathogenic comparator exists at codon 483, so PM1 and PM5 are not met. No de novo, segregation, or case-control data are available for germline RASopathy. Functional data from the cancer literature classifies K483E as a Class 3 BRAF mutation (kinase-impaired, activates ERK via CRAF transactivation), but this has not been tested in VCEP-approved assays. No benign criteria are met. With two supporting pathogenic criteria (PP2, PP3) and no criteria at moderate or strong level, the variant does not meet any VCEP pathogenic or likely pathogenic classification rule. Per VCEP framework rules, the variant remains a Variant of Uncertain Significance.

Met · 2

PP2 SupportingBRAF is a gene with a low rate of benign missense variation and where missense variants are a common mechanism of disease. The RASopathy VCEP applies PP2 at supporting strength when the gene's missense z-score exceeds 3.09 in gnomAD. BRAF has a well-established high missense constraint (missense z-score significantly > 3.09), consistent with a gene where missense variation is a common disease mechanism in RASopathies. Details ▾Hide ▴

Evidence considered

BRAF missense z-score exceeds 3.09 in gnomAD (VCEP PP2 rule)
Missense variants are a well-established mechanism in RASopathies

Sources

cspec ↗

PP3 SupportingThe VCEP applies PP3 at supporting strength for missense variants when REVEL score is at least 0.7. The REVEL score for NM_004333.5:c.1447A>G (p.Lys483Glu) is 0.973, well above the threshold, indicating a strong in silico prediction of deleterious effect. SpliceAI predicts no splicing impact (max delta = 0.00), consistent with an amino-acid-level deleterious effect. Details ▾Hide ▴

Evidence considered

REVEL score: 0.973 (≥ 0.7 VCEP threshold)
SpliceAI max delta: 0.00 (no splicing impact)

Sources

revelspliceai ↗cspec ↗

Not met · 16 · evaluated, threshold not reached

PS1 No evidence that the same amino acid change (p.Lys483Glu) has been previously established as pathogenic. K483E is classified as Variant of Uncertain Significance in ClinVar (single submitter, Invitae) and is not listed as pathogenic/likely pathogenic by any expert panel. Details ▾Hide ▴

Evidence considered

ClinVar classification: Uncertain significance (VariationID 1418218
single submitter)

Sources

clinvar ↗

PS2 No de novo observation data are available for this variant. No publications or clinical records report a confirmed de novo occurrence with maternity and paternity confirmed. Details ▾Hide ▴

Still missing

No de novo segregation data available for this variant

PS3 Functional data from the cancer literature demonstrates that BRAF K483E is a Class 3 mutation with impaired kinase activity that activates ERK signaling through CRAF transactivation (Owsley 2020, Kondo 2020). However, the ClinGen RASopathy VCEP PS3 criterion requires testing in VCEP-approved functional assays (MEK Activation, ERK Activation, or BRAF Kinase Activity assays as specified in the supplemental SVI-RASopathy-VCEP-V2-Approved-Functional-Studies spreadsheet). K483E has not been tested in any of these approved assays. The existing functional data, while informative, does not meet the VCEP PS3 evidence threshold. Details ▾Hide ▴

Evidence considered

K483E classified as Class 3 (kinase-impaired) in Owsley 2020 cohort (14 occurrences)
K483E PDO showed elevated basal ERK and paradoxical activation by encorafenib in Kondo 2020
K483E construct generated and tested in O'Farrell 2016 (cancer context
not VCEP-approved assay)

Still missing

No VCEP-approved functional assay data for K483E
Functional data from cancer context
germline RASopathy relevance uncertain

Sources

PMID:33019809 ↗PMID:33060766 ↗PMID:27799065 ↗

PS4 No case-control data or proband counts are available in the context of RASopathy. The variant has been observed in somatic cancer cohorts (COSMIC: 19 samples; Owsley 2020: 14 occurrences), but these are cancer/somatic cases and do not constitute germline RASopathy proband evidence. Details ▾Hide ▴

Evidence considered

COSMIC COSV56236813: 19 somatic cancer samples
Owsley 2020: 14 occurrences in cancer genomics database

Still missing

No germline RASopathy proband counts available

Sources

PMID:33019809 ↗

PM1 The VCEP defines PM1 as applicable only to specific functional domains: P-loop (AA 459-474) and CR3 activation segment (AA 594-627). The variant p.Lys483Glu (position 483) lies between these domains and is not within a VCEP-recognized critical functional domain. The variant is also not at a statistically significant hotspot (cancerhotspots.org). Details ▾Hide ▴

Evidence considered

Position 483 is outside VCEP-defined domains (P-loop 459-474
CR3 594-627)
Not at a statistically significant cancer hotspot

Sources

cspec ↗

PM2 The RASopathy VCEP requires the variant to be absent from gnomAD controls. NM_004333.5:c.1447A>G is present in gnomAD v2.1 (1/251,326 alleles; AF=3.98e-6) and gnomAD v4.1 (1/1,613,408 alleles; AF=6.20e-7). While at extremely low frequency, it is not absent, and thus the VCEP PM2 criterion is not satisfied. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: 1/251
326 alleles (AF=3.98e-6)
gnomAD v4.1: 1/1
613
408 alleles (AF=6.20e-7)

Sources

gnomad_v2 ↗gnomad_v4 ↗

PM5 No [likely] pathogenic missense variant at codon 483 other than the variant under assessment has been identified. ClinVar has no P/LP entries for any alternative amino acid change at position 483. No same-codon comparator variants were identified in the PM5 candidate search. Details ▾Hide ▴

Evidence considered

No P/LP variant at codon 483 in ClinVar
PM5 candidate search returned zero same-residue candidates

Sources

pm5_candidates

PM6 No assumed de novo data are available. No publications report this variant as a presumed de novo occurrence without confirmation of maternity and paternity. Details ▾Hide ▴

Still missing

No de novo or assumed de novo data available

PP1 No co-segregation data are available. The VCEP requires at least 3 informative meioses for supporting strength. No family studies or segregation analyses have been reported for this variant. Details ▾Hide ▴

Still missing

No segregation data available

BA1 The VCEP BA1 threshold is an allele frequency of at least 0.05% in gnomAD. The variant frequency is 0.0004% in gnomAD v2.1 and 0.00006% in gnomAD v4.1, far below the stand-alone benign threshold. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF: 0.0004% (threshold 0.05%
not met)
gnomAD v4.1 AF: 0.00006%

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 The VCEP BS1 threshold is an allele frequency of at least 0.025% in gnomAD. The variant frequency is far below this threshold (0.0004% in v2.1, 0.00006% in v4.1). Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF: 0.0004% (threshold 0.025%
not met)
gnomAD v4.1 AF: 0.00006%

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 No data are available regarding observation of this variant in healthy adult individuals for a dominant disorder expected to be fully penetrant at an early age. Details ▾Hide ▴

Still missing

No healthy adult carrier data available

BS4 No segregation data are available to demonstrate lack of segregation in affected family members. The VCEP requires only one informative meiosis for strong benign evidence, but no such data exist. Details ▾Hide ▴

Still missing

No segregation data available

BP2 No data are available regarding an alternative molecular cause of a RASopathy in the same gene (e.g., observation in trans with a pathogenic variant). The point-based scoring system requires at least -1 point for supporting strength, and no such evidence exists. Details ▾Hide ▴

Still missing

No data on alternative molecular cause in BRAF

BP4 The VCEP BP4 threshold for missense variants is REVEL score at most 0.3. The REVEL score for p.Lys483Glu is 0.973, which is strongly in the pathogenic range and does not satisfy the benign computational evidence threshold. Additionally, SpliceAI predicts no splice impact (max delta 0.00), but the REVEL score alone precludes BP4 application. Details ▾Hide ▴

Evidence considered

REVEL score: 0.973 (> 0.3 threshold
BP4 not met)
SpliceAI max delta: 0.00 (no splicing alteration)

Sources

revelspliceai ↗cspec ↗

BP5 No data are available regarding an alternative molecular cause of a RASopathy in a different gene, or a phenotype inconsistent with a RASopathy and fully explained by a different causative variant. Details ▾Hide ▴

Still missing

No data on alternative molecular cause in other genes

Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 VCEPNM_004333.5:c.1447A>G is a missense variant (p.Lys483Glu). PVS1 is defined for null variants (nonsense, frameshift, canonical splice sites) and is explicitly marked as not applicable by the ClinGen RASopathy VCEP for BRAF v2.3.0. Details ▾Hide ▴

Evidence considered

VCEP rule: PVS1 applicability is Not applicable for BRAF RASopathy framework

Sources

cspec ↗

PM3 VCEPRASopathies are autosomal dominant disorders; PM3 (in trans with pathogenic for recessive disorders) is not applicable. Details ▾Hide ▴

No further detail was recorded.

PM4 N/ASubstitution variant; PM4 applies only to protein-length-altering variants (in-frame indels, stop-loss). Details ▾Hide ▴

No further detail was recorded.

PP4 VCEPThe ClinGen RASopathy VCEP marks PP4 as not applicable; see PS4 instead for phenotype-based evidence. Details ▾Hide ▴

Evidence considered

VCEP rule: PP4 applicability is Not applicable

Sources

cspec ↗

PP5 VCEPThe ClinGen RASopathy VCEP explicitly states that PP5 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴

Evidence considered

VCEP rule: PP5 applicability is Not Applicable for this VCEP

Sources

cspec ↗

BS3 VCEPThe ClinGen RASopathy VCEP lists BS3 as not applicable. The criterion for well-established functional studies showing no damaging effect is not implemented in this framework. Details ▾Hide ▴

Evidence considered

VCEP rule: BS3 applicability is Not applicable

Sources

cspec ↗

BP1 N/AThe VCEP BP1 rule is specific to truncating variants in genes where the disease mechanism is gain-of-function. NM_004333.5:c.1447A>G is a missense variant (p.Lys483Glu), not a truncating variant. BP1 does not apply to missense variants in this framework. Details ▾Hide ▴

Evidence considered

BP1 VCEP rule applies only to truncating variants
this is a missense variant

Sources

cspec ↗

BP3 VCEPSubstitution variant; BP3 applies only to in-frame deletions/insertions in repetitive regions. Details ▾Hide ▴

No further detail was recorded.

BP6 VCEPThe ClinGen RASopathy VCEP explicitly states that BP6 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴

Evidence considered

VCEP rule: BP6 applicability is Not Applicable for this VCEP

Sources

cspec ↗

BP7 N/ABP7 applies to synonymous (silent) variants with no predicted splice impact. NM_004333.5:c.1447A>G is a missense variant resulting in p.Lys483Glu and is not a synonymous variant. Details ▾Hide ▴

Evidence considered

BP7 applies only to synonymous variants
this is a missense variant

PS5 N/APS5 is not a criterion defined in the ClinGen RASopathy VCEP framework for BRAF v2.3.0, nor is it a standard ACMG/AMP 2015 criterion (Richards et al., PMID:25741868). No VCEP rule references PS5. Details ▾Hide ▴

Evidence considered

PS5 not defined in VCEP criteria set or standard ACMG/AMP 2015

Sources

cspec ↗

Identifiers

Gene: BRAF
Transcript: NM_004333.5
Coding (HGVS c.): NM_004333.5:c.1447A>G
Protein (HGVS p.): NP_004324.2:p.(Lys483Glu)
GRCh38: chr7:140778061 T>C
GRCh37: chr7:140477861 T>C
ClinVar: 1418218
COSMIC: COSV56236813

Gene diagram

Every interpreted variant in BRAF, mapped onto the exon structure of NM_004333.5. Select a row to find it on the plot.

BRAFNM_004333.5

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 BRAF — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 1 / 1,613,408 alleles AF 6.2e-07 · 0 homozygotes

gnomAD v2.1 1 / 251,326 alleles AF 3.98e-06 · 0 homozygotes

gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 6.2e-07 · 1 / 1,613,408 alleles · 0 hom

Admixed American1 / 60,012

1.7e-05

0 alternate alleles recorded in 9 other groups: Remaining individuals, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish).

gnomAD v2.1

AF 4e-06 · 1 / 251,326 alleles · 0 hom

Admixed American1 / 34,552

2.9e-05

0 alternate alleles recorded in 7 other groups: African/African American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 6.19806e-07; MAF= 0.00006%, 1/1613408 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 1.66633e-05; MAF= 0.00167%, 1/60012 alleles, homozygotes = 0).

gnomAD v2.1

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat +31 bp

0.000

SpliceAI acceptor gainat +14 bp

0.000

SpliceAI donor lossat +2 bp

0.000

SpliceAI donor gainat -70 bp

0.000

Pangolin splice lossmagnitude shown

-0.000

Pangolin splice gain

0.000

Other predictors

REVEL: 0.973
BayesDel: 0.580

How the predictions were used

Evidence considered

REVEL score: 0.973 (≥ 0.7 VCEP threshold)
SpliceAI max delta: 0.00 (no splicing impact)

Sources

revelspliceai ↗cspec ↗

Evidence considered

REVEL score: 0.973 (> 0.3 threshold
BP4 not met)
SpliceAI max delta: 0.00 (no splicing alteration)

Sources

revelspliceai ↗cspec ↗

Evidence considered

BP7 applies only to synonymous variants
this is a missense variant

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.973. BayesDel score = 0.579862.

3 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.

Recorded publications

A case study of an integrative genomic and experimental therapeutic approach for rare tumors: identification of vulnerabilities in a pediatric poorly differentiated carcinoma.

Case study of a pediatric poorly differentiated carcinoma. BRAF K483E was identified in the tumor alongside CTNNB1, MAX, and MYCN alterations. A FLAG-tagged BRAF-K483E construct was generated and tested in BRAF-/- MEFs. The study focused on therapeutic response to selumetinib (MEK inhibitor) and mTOR inhibition in patient-derived xenograft models. The variant was evaluated in a somatic cancer context, not a germline RASopathy setting.
Names this variant
PMID 27799065 ↗
Quoted passage
pBabe-bleo-Flag-BRAF-WT and pBABEbleo-FLAG-BRAF-K483E were generated by gene synthesis and cloning (GenScript, Piscataway, NJ, USA).
Methods: Transfection and retroviral transduction section; plasmid construction details
Prevalence of class I-III BRAF mutations among 114,662 cancer patients in a large genomic database.

Large cohort study of 114,662 cancer patients with comprehensive genomic profiling. K483E classified as a Class 3 BRAF mutation (kinase-impaired/low kinase activity compared to wild type, activates MAPK pathway through enhanced RAS binding and CRAF transactivation). Reported 14 occurrences across the cohort, representing 1.7% of Class 3 BRAF mutations.
Names this variant
PMID 33019809 ↗
Quoted passage
K483E | 3 | 14
Table 1 (Class 3 mutations listing); Results section
Evaluation of the RAS signaling network in response to MEK inhibition using organoids derived from a familial adenomatous polyposis patient.

Evaluation of RAS signaling in patient-derived organoids from a familial adenomatous polyposis patient. PDO HCT70-6P harboring BRAF K483E showed elevated basal ERK phosphorylation, paradoxical increase in cell viability upon encorafenib (BRAF inhibitor) treatment consistent with Class 3 behavior, and hypersensitivity to binimetinib (MEK inhibitor). The authors conclude BRAF K483E is an activating mutation of RAS signaling with effects mediated through allosteric activation of its dimer partner (CRAF).
Names this variant
PMID 33060766 ↗
Quoted passage
Dela Cruz et al. reported that BRAF K483E expression potentiated ERK activation although it harbors a catalytically dead kinase domain.
Results section (Drug responses of PDOs, paragraph on encorafenib and binimetinib responses); Discussion

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 1 / 1,613,408 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 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 ↗

ClinGen CSpec Captured ClinGen CSpec 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

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 = 1418218)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.973. BayesDel score = 0.579862.

Functional

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely 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; COSV56236813, n = 19 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.