About BRAF
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRAF c.736G>C, p.(Ala246Pro)
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 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: 7
Benign evidence criteria: 0
Pathogenic criteria applied · 7
PS4Supporting
PS4 · supporting
This variant has been observed in multiple unrelated probands with cardio-facio-cutaneous (CFC) syndrome / RASopathy phenotype. It was identified among 8 BRAF mutations in 16 individuals from the original CFC cohort (Niihori et al. 2006). Nine independent clinical laboratories have submitted this variant as Pathogenic to ClinVar, and the ClinGen RASopathy VCEP has classified it as Pathogenic (VariationID 13965). The aggregate observation across multiple independent probands supports PS4 at a supporting level.
PM1Moderate
PM1 · moderate
The variant c.736G>C lies within exon 6 (c.712-860), which is one of the critical and well-established functional domains defined by the ClinGen RASopathy VCEP v2.3.0 (along with exon 11, P-loop AA 459-474, and CR3 activation segment AA 594-627). Exon 6 encodes part of the cysteine-rich domain (CRD) critical for BRAF function. The variant is absent from gnomAD, meeting the requirement of no benign variation in the domain.
PM2Supporting
PM2 · supporting
The variant is absent from gnomAD v2.1 and v4.1 population databases. Per the RASopathy VCEP v2.3.0, PM2 is applied at supporting strength when the variant is absent from gnomAD controls.
PM6Supporting
PM6 · supporting
Niihori et al. 2006 (PMID:16474404) reported a de novo occurrence of BRAF c.736G>C (p.Ala246Pro) in a proband with CFC syndrome where both parents tested negative for the variant. However, formal maternity/paternity confirmation was not performed, satisfying PM6 (assumed de novo without confirmed parentage) at supporting level (0.5 points) per the RASopathy VCEP point-based scoring system.
PP2Supporting
PP2 · supporting
BRAF has a high gnomAD missense z-score (well above 3.09), indicating strong constraint against missense variation in the general population. Missense variants are a common mechanism of disease for BRAF (gain-of-function in RASopathies). Per the RASopathy VCEP v2.3.0, PP2 is met at supporting strength when the gene's missense z-score exceeds 3.09 in gnomAD.
PP3Supporting
PP3 · supporting
The REVEL score for this missense variant is 0.928, which exceeds the threshold of ≥0.7 specified by the RASopathy VCEP v2.3.0 for PP3 at supporting strength. Multiple in silico tools support a deleterious effect on protein function.
PP5Supporting
PP5 · supporting
Expert panel ClinGen RASopathy Variant Curation Expert Panel classified as Pathogenic.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Likely pathogenic
ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRAF Version 2.3.0 v2.3.0 criteria-combination framework: matched Rule15 (1 Pathogenic.Moderate + Pathogenic.Supporting >=4) with applied criteria: PS4 supporting, PM1 moderate, PM2 supporting, PM6 supporting, PP2 supporting, PP3 supporting, PP5 supporting; 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.
SpliceAI score
0.050 maximum delta
Recorded SpliceAI maximum delta score: 0.050. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
9 reported laboratory submissions
9 Pathogenic.
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
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
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: 7 met · 5 not met · 7 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The BRAF c.736G>C (p.Ala246Pro) missense variant is absent from gnomAD population databases (PM2_Supporting).
The variant lies within exon 6, a critical functional domain defined by the ClinGen RASopathy VCEP v2.3.0 (PM1_Moderate).
The variant has been observed in multiple unrelated probands with cardio-facio-cutaneous syndrome, including the original CFC discovery cohort (Niihori et al. 2006), and is classified as Pathogenic by the ClinGen RASopathy VCEP in ClinVar with submissions from 9 clinical laboratories (PS4_Supporting).
A de novo occurrence was reported in a CFC proband with both parents negative, though without molecular confirmation of parentage (PM6_Supporting).
In silico predictions support a deleterious effect: REVEL score is 0.928, exceeding the VCEP threshold of 0.7 (PP3).
BRAF exhibits a high gnomAD missense z-score (>3.09), indicating constraint against missense variation, and missense variants are a common disease mechanism for RASopathies (PP2).
Functional studies by Wen et al. 2013 demonstrated that A246P increases Ras binding affinity relative to wild-type, consistent with a gain-of-function mechanism, though the assay is not in the VCEP-approved functional studies list (PS3 not assessed).
Under the ClinGen RASopathy VCEP v2.3.0 combination rules (Rule15: 1 moderate + ≥4 supporting → Likely Pathogenic), the variant meets PM1 (moderate) plus PM2_Supporting, PM6_Supporting, PS4_Supporting, PP2, and PP3 (5 supporting criteria), resulting in a classification of Likely Pathogenic.
No criteria match.
Met · 7
PS4 SupportingThis variant has been observed in multiple unrelated probands with cardio-facio-cutaneous (CFC) syndrome / RASopathy phenotype. It was identified among 8 BRAF mutations in 16 individuals from the original CFC cohort (Niihori et al. 2006). Nine independent clinical laboratories have submitted this variant as Pathogenic to ClinVar, and the ClinGen RASopathy VCEP has classified it as Pathogenic (VariationID 13965). The aggregate observation across multiple independent probands supports PS4 at a supporting level. Details ▾Hide ▴
Evidence considered
- Reported in multiple CFC probands (Niihori 2006)
- ClinVar: 9 clinical labs + expert panel classification as Pathogenic
- PMID:24409384 reports A246P as a CFC-causing mutant
Still missing
- Exact proband count not determined
- VCEP evidence packet may contain precise numbers that could elevate PS4 to moderate or strong
Sources
PM1 ModerateThe variant c.736G>C lies within exon 6 (c.712-860), which is one of the critical and well-established functional domains defined by the ClinGen RASopathy VCEP v2.3.0 (along with exon 11, P-loop AA 459-474, and CR3 activation segment AA 594-627). Exon 6 encodes part of the cysteine-rich domain (CRD) critical for BRAF function. The variant is absent from gnomAD, meeting the requirement of no benign variation in the domain. Details ▾Hide ▴
Evidence considered
- c.736 is within exon 6 (CSPEC-defined critical domain)
- Variant absent from gnomAD v2.1 and v4.1
Sources
PM2 SupportingThe variant is absent from gnomAD v2.1 and v4.1 population databases. Per the RASopathy VCEP v2.3.0, PM2 is applied at supporting strength when the variant is absent from gnomAD controls. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (exomes)
- Absent from gnomAD v4.1 (exomes/genomes)
Sources
PM6 SupportingNiihori et al. 2006 (PMID:16474404) reported a de novo occurrence of BRAF c.736G>C (p.Ala246Pro) in a proband with CFC syndrome where both parents tested negative for the variant. However, formal maternity/paternity confirmation was not performed, satisfying PM6 (assumed de novo without confirmed parentage) at supporting level (0.5 points) per the RASopathy VCEP point-based scoring system. Details ▾Hide ▴
Evidence considered
- Niihori et al. 2006: de novo A246P in CFC proband
- parents negative
- parentage not confirmed
Still missing
- Parentage not molecularly confirmed
- if confirmed
- would upgrade to PS2
- Additional assumed de novo reports may exist but were not verified at abstract level
Sources
PMID:16474404 ↗16474404
PP2 SupportingBRAF has a high gnomAD missense z-score (well above 3.09), indicating strong constraint against missense variation in the general population. Missense variants are a common mechanism of disease for BRAF (gain-of-function in RASopathies). Per the RASopathy VCEP v2.3.0, PP2 is met at supporting strength when the gene's missense z-score exceeds 3.09 in gnomAD. Details ▾Hide ▴
Evidence considered
- BRAF gnomAD missense z-score >3.09
- Missense variants are the predominant disease mechanism in BRAF-related RASopathies
Sources
PP3 SupportingThe REVEL score for this missense variant is 0.928, which exceeds the threshold of ≥0.7 specified by the RASopathy VCEP v2.3.0 for PP3 at supporting strength. Multiple in silico tools support a deleterious effect on protein function. Details ▾Hide ▴
Evidence considered
- REVEL score = 0.928 (≥0.7 threshold met)
- SpliceAI max delta = 0.05 (no significant splicing impact)
Sources
revelcspec ↗
Not met · 5 · evaluated, threshold not reached
PS1 PS1 requires the same amino acid change to have been previously established as pathogenic through a different nucleotide change. The c.736G>C (p.Ala246Pro) variant is itself the variant that established A246P as pathogenic; no evidence of a different nucleotide change producing A246P was identified. The CSPEC rule also allows cross-gene analogy with RAF1, but no data on an analogous RAF1 variant was available. Details ▾Hide ▴
Evidence considered
- A246P is the known pathogenic change established by this variant
- no prior different nucleotide change exists
Still missing
- No evidence of a different nucleotide change causing the same A246P amino acid change
- No RAF1 analogous residue data assessed
PS2 PS2 requires de novo occurrence with both maternity and paternity confirmed. Niihori et al. 2006 (PMID:16474404) reported a de novo observation of BRAF c.736G>C (p.Ala246Pro) in a CFC proband with both parents negative, but formal maternity/paternity confirmation was not performed. Without molecular confirmation of parentage, PS2 cannot be applied. Details ▾Hide ▴
Evidence considered
- Niihori et al. 2006 reported de novo A246P in CFC proband
- parents negative but parentage not molecularly confirmed
Still missing
- No confirmed de novo reports with maternity/paternity testing
- Additional publications (PMID:18042262
- PMID:17704260) may contain de novo data but were not verified at variant level
Sources
PMID:16474404 ↗16474404
BA1 BA1 requires a gnomAD filtering allele frequency ≥0.05%. This variant is absent from both gnomAD v2.1 and v4.1, so BA1 is not met. Details ▾Hide ▴
Evidence considered
- Variant absent from gnomAD v2.1
- Variant absent from gnomAD v4.1
Sources
BS1 BS1 requires a gnomAD filtering allele frequency ≥0.025% per the RASopathy VCEP v2.3.0. This variant is absent from both gnomAD v2.1 and v4.1, so BS1 is not met. Details ▾Hide ▴
Evidence considered
- Variant absent from gnomAD v2.1
- Variant absent from gnomAD v4.1
Sources
BP4 BP4 requires a REVEL score ≤0.3 for missense variants per the RASopathy VCEP v2.3.0. The REVEL score for this variant is 0.928, which is strongly in the pathogenic range and does not meet the BP4 threshold. Details ▾Hide ▴
Not assessed · 7 · no assessment recorded
PS3 Functional evidence for this variant exists in the literature. Wen et al. 2013 (PMID:24409384) demonstrated that BRAF A246P exhibits increased Ras binding affinity relative to wild-type using optical tweezers single-molecule force measurements. However, this assay (optical tweezers / Ras binding kinetics) is not among the VCEP-approved functional assays (RAS Activation, MEK Activation, ERK Activation, BRAF Kinase Activity, RAF1 Kinase Activity, SHP-2 Phosphatase, LZTR1 Stability). Without testing in a VCEP-approved assay, PS3 cannot be applied under the RASopathy VCEP framework. Details ▾Hide ▴
Evidence considered
- PMID:24409384 shows A246P increases Ras binding affinity (gain-of-function)
- but assay not in VCEP-approved list
Still missing
- No evidence of this variant tested in VCEP-approved functional assays (BRAF Kinase Activity
- MEK Activation
- ERK Activation)
- PMID:19376813 may contain zebrafish functional data but specific variant mention not confirmed at abstract level
Sources
PMID:24409384 ↗24409384
PM5 PM5 requires at least one different [likely] pathogenic residue change at the same codon (Ala246). The PM5 candidate screen identified zero comparator variants at residue 246 in ClinVar or other sources. The CSPEC also allows cross-gene analogy with RAF1, but no data on RAF1 residue 246 comparators was available. Without a comparator variant, PM5 cannot be applied. Details ▾Hide ▴
Evidence considered
- No pathogenic missense variants at BRAF residue 246 other than A246P identified
- PM5 candidate search returned 0 results
Still missing
- No other missense changes at codon 246 identified in ClinVar or literature
- RAF1 analogous residue not assessed
PP1 No cosegregation data were identified for this variant. Most RASopathy cases with BRAF mutations are sporadic, and multigenerational families with this variant are rare. PP1 requires at least 3 informative meioses for supporting level. Details ▾Hide ▴
Still missing
- No cosegregation data available
- Familial BRAF A246P cases are rare given dominant inheritance with reduced reproductive fitness
BS2 BS2 requires observation of the variant in a healthy adult individual. No evidence of this variant being found in healthy adults was identified. Given that this variant is associated with an early-onset developmental disorder and is absent from gnomAD, BS2 is unlikely to be met. Details ▾Hide ▴
Still missing
- No systematic search for unaffected carriers performed
BS4 BS4 requires lack of segregation in affected family members. No nonsegregation data were identified. Given that this variant is well-established as pathogenic in CFC syndrome, nonsegregation evidence is unlikely to exist. Details ▾Hide ▴
Still missing
- No nonsegregation data identified
- Given pathogenic nature of variant
- BS4-defining evidence is unlikely to exist
BP2 BP2 requires observation of the variant in trans with a pathogenic variant in the same gene, or an alternative molecular cause of a RASopathy. No evidence of the variant occurring in trans with another BRAF pathogenic variant in an unaffected individual was identified. Details ▾Hide ▴
Still missing
- No trans configuration data identified
BP5 BP5 requires an alternative molecular cause of a RASopathy in a different gene, with phenotype consistent with expected severity. No evidence of an alternative molecular cause was identified for probands carrying this variant. Details ▾Hide ▴
Still missing
- No data on alternative molecular causes in probands with this variant
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 VCEPPVS1 is not applicable per the ClinGen RASopathy VCEP v2.3.0 specifications for BRAF; this criterion is reserved for null variants (nonsense, frameshift, canonical splice) and is not intended for missense variants in this framework. Details ▾Hide ▴
Evidence considered
- CSPEC rule: PVS1 applicability = Not Applicable for BRAF RASopathy VCEP v2.3.0
Sources
PM3 VCEPSKIPPED per user instruction: trivially not applicable. PM3 is also listed as not applicable per the ClinGen RASopathy VCEP v2.3.0 (recessive disorder criterion; RASopathies are autosomal dominant). Details ▾Hide ▴
No further detail was recorded.
PM4 N/ASKIPPED per user instruction: trivially not applicable. This variant is a single nucleotide substitution, not an in-frame deletion/insertion or stop-loss variant. Details ▾Hide ▴
No further detail was recorded.
PP4 VCEPPP4 is not applicable per the ClinGen RASopathy VCEP v2.3.0. The VCEP directs users to use PS4 instead for phenotype specificity. Details ▾Hide ▴
BS3 VCEPBS3 is not applicable per the ClinGen RASopathy VCEP v2.3.0 specifications for BRAF. Details ▾Hide ▴
BP1 N/ABP1 applies only to truncating variants (nonsense, frameshift, canonical splice) in genes where the disease mechanism is primarily gain-of-function missense. This variant is a missense substitution (c.736G>C, p.Ala246Pro) and therefore BP1 is not applicable. Details ▾Hide ▴
Evidence considered
- Variant is missense (Ala246Pro)
- not truncating
- CSPEC BP1 rule restricts application to truncating variants
Sources
BP3 VCEPSKIPPED per user instruction: trivially not applicable. BP3 is also listed as not applicable per the ClinGen RASopathy VCEP v2.3.0. Details ▾Hide ▴
No further detail was recorded.
BP6 VCEPBP6 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee per the RASopathy VCEP v2.3.0. Details ▾Hide ▴
Evidence considered
- CSPEC rule: BP6 is not for use per ClinGen SVI VCEP Review Committee recommendation
Sources
BP7 N/ABP7 applies only to synonymous (silent) variants with no predicted splice impact. This variant is a missense substitution (c.736G>C, p.Ala246Pro) and therefore BP7 is not applicable. Details ▾Hide ▴
Evidence considered
- Variant is missense (Ala246Pro)
- not synonymous
PS5 N/APS5 is not defined in the ClinGen RASopathy VCEP v2.3.0 specifications for BRAF. The VCEP framework does not include this criterion. Details ▾Hide ▴
Identifiers
- Gene
- BRAF
- Transcript
- NM_001354609.1
- Coding (HGVS c.)
- NM_001354609.1:c.736G>C
- Protein (HGVS p.)
- NP_001341538.1:p.(Ala246Pro)
- GRCh38
- chr7:140801536 C>G
- GRCh37
- chr7:140501336 C>G
- ClinVar
- 13965
Gene diagram
Every interpreted variant in BRAF, mapped onto the exon structure of NM_001354609.1. Select a row to find it on the plot.
BRAFNM_001354609.1
Fetching transcript structure from UCSC…
Exons
—
Transcript span
—
Strand
—
Variants mapped
—
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
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.928
- BayesDel
- 0.461
How the predictions were used
PP3 SupportingThe REVEL score for this missense variant is 0.928, which exceeds the threshold of ≥0.7 specified by the RASopathy VCEP v2.3.0 for PP3 at supporting strength. Multiple in silico tools support a deleterious effect on protein function. Details ▾Hide ▴
Evidence considered
- REVEL score = 0.928 (≥0.7 threshold met)
- SpliceAI max delta = 0.05 (no significant splicing impact)
Sources
revelcspec ↗
BP4 BP4 requires a REVEL score ≤0.3 for missense variants per the RASopathy VCEP v2.3.0. The REVEL score for this variant is 0.928, which is strongly in the pathogenic range and does not meet the BP4 threshold. Details ▾Hide ▴
BP7 N/ABP7 applies only to synonymous (silent) variants with no predicted splice impact. This variant is a missense substitution (c.736G>C, p.Ala246Pro) and therefore BP7 is not applicable. Details ▾Hide ▴
Evidence considered
- Variant is missense (Ala246Pro)
- not synonymous
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05). REVEL score = 0.928. BayesDel score = 0.460772.
8 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
-
PMID 16474404 ↗Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome.Niihori T et al. · 2006No paper-specific finding is recorded.
-
PMID 19376813 ↗Kinase-activating and kinase-impaired cardio-facio-cutaneous syndrome alleles have activity during zebrafish development and are sensitive to small molecule inhibitors.Anastasaki C et al. · 2009No paper-specific finding is recorded.
-
PMID 24409384 ↗Single-molecule force measurement via optical tweezers reveals different kinetic features of two BRaf mutants responsible for cardio-facial-cutaneous (CFC) syndrome.No paper-specific finding is recorded.
-
PMID 18042262 ↗Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.Schulz AL et al. · 2008No paper-specific finding is recorded.
-
PMID 24033266 ↗A systematic approach to assessing the clinical significance of genetic variants.No paper-specific finding is recorded.
-
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.No paper-specific finding is recorded.
-
PMID 25173338 ↗2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).No paper-specific finding is recorded.
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
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 0.050
Open source ↗
ClinVar
9 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 ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/643243119
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/13965/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/7-140501336-C-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr7-140801536-C-G?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_001354609.1%3Ac.7…
- OncoKB ↗www.oncokb.org/gene/BRAF/A246P
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRAF+c.736G%3EC
- 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.
ClinVar
This variant has been reported in ClinVar as Pathogenic (9 clinical laboratories) and as Pathogenic by ClinGen RASopathy Variant Curation Expert Panel (expert panel). (ClinVarID = 13965)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05). REVEL score = 0.928. BayesDel score = 0.460772.
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 not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.