About NRAS
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
NRAS c.34G>T, p.(Gly12Cys)
Classification
Pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.
Pathogenic.A 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 NRAS 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: 5
Benign evidence criteria: 0
Pathogenic criteria applied · 5
PS1Strong
PS1 · strong
The variant produces p.Gly12Cys in NRAS, which is a well-established pathogenic amino acid change at codon 12 in RAS genes. The same residue (G12) is a recurrent oncogenic hotspot, and multiple NRAS G12 missense changes are classified as pathogenic. The RASopathy VCEP v2.3.0 assigns PS1 at Strong when the same amino acid change has been previously established as pathogenic, applicable across HRAS, KRAS, MRAS, NRAS, RIT1, and RRAS2.
PM1Moderate
PM1 · moderate
The variant affects codon 12 (p.Gly12Cys), which lies within the P-loop (amino acids 10-17), a critical and well-established functional domain recognized by the RASopathy VCEP. Codon 12 is a statistically significant mutational hotspot without benign variation.
PM2Supporting
PM2 · supporting
The variant is absent from all gnomAD population datasets (v2.1, v4.1, and gnomAD-Canada v1.0), satisfying the RASopathy VCEP requirement that the variant must be absent from controls.
PM5Moderate
PM5 · moderate
At least one other pathogenic missense change at the same codon (G12) has been established in NRAS. NRAS G12D, G12V, G12S, G12A, and G12R are well-documented pathogenic variants in both somatic and germline contexts. The RASopathy VCEP assigns PM5 at Moderate strength when one [likely] pathogenic residue change exists at the same codon.
PP3Supporting
PP3 · supporting
The REVEL score for this missense variant is 0.773, which meets the RASopathy VCEP threshold of ≥0.7 for PP3 at Supporting strength. SpliceAI predicts no splice impact (max delta = 0.00), consistent with a missense effect.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Pathogenic
ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for NRAS Version 2.3.0 v2.3.0 criteria-combination framework: matched Rule7 (1 Pathogenic.Strong + 2 Pathogenic.Moderate + Pathogenic.Supporting >=2) with applied criteria: PS1 strong, PM1 moderate, PM2 supporting, PM5 moderate, PP3 supporting; maps to Pathogenic.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
2 reported laboratory submissions
2 Pathogenic.
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
273 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV54736487, n = 273 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen NRAS VCEP v2.3.0, with the data and sources behind each one.
29 criteria with recorded statuses: 5 met · 3 not met · 9 not assessed · 12 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_002524.4:c.34G>T (p.Gly12Cys) in NRAS is a missense variant affecting codon 12 in the P-loop (AA 10-17), a critical GTP-binding domain recognized by the RASopathy VCEP.
The p.Gly12Cys amino acid change is a well-established pathogenic alteration in NRAS and homologous RAS genes, meeting PS1 at Strong strength.
The variant lies within the P-loop functional domain (PM1, Moderate) and represents a missense change at a codon where other pathogenic missense variants are established (PM5, Moderate).
The variant is absent from all gnomAD population databases, meeting PM2 at Supporting strength.
REVEL score of 0.773 supports a deleterious effect, meeting PP3 at Supporting strength.
No de novo, cosegregation, case-count, or functional assay data from VCEP-approved platforms were available for this variant; PS2, PS3, PS4, PM6, PP1, BS2, BS4, BP2, and BP5 remain unassessed.
No criteria match.
Met · 5
PS1 StrongThe variant produces p.Gly12Cys in NRAS, which is a well-established pathogenic amino acid change at codon 12 in RAS genes. The same residue (G12) is a recurrent oncogenic hotspot, and multiple NRAS G12 missense changes are classified as pathogenic. The RASopathy VCEP v2.3.0 assigns PS1 at Strong when the same amino acid change has been previously established as pathogenic, applicable across HRAS, KRAS, MRAS, NRAS, RIT1, and RRAS2. Details ▾Hide ▴
Evidence considered
- ClinVar classifies NRAS G12C as Pathogenic (VariationID 40468
- 2 clinical laboratories).
- OncoKB classifies NRAS G12C as Likely Oncogenic.
- G12 is a recurrent oncogenic hotspot across RAS genes with extensive supporting literature.
Still missing
- ClinVar review status is 1-star (criteria provided
- single submitter)
- no expert panel submission.
Sources
PM1 ModerateThe variant affects codon 12 (p.Gly12Cys), which lies within the P-loop (amino acids 10-17), a critical and well-established functional domain recognized by the RASopathy VCEP. Codon 12 is a statistically significant mutational hotspot without benign variation. Details ▾Hide ▴
PM2 SupportingThe variant is absent from all gnomAD population datasets (v2.1, v4.1, and gnomAD-Canada v1.0), satisfying the RASopathy VCEP requirement that the variant must be absent from controls. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (exomes).
- Absent from gnomAD v4.1 (exomes).
- Absent from gnomAD-Canada v1.0 (genomes).
Sources
PM5 ModerateAt least one other pathogenic missense change at the same codon (G12) has been established in NRAS. NRAS G12D, G12V, G12S, G12A, and G12R are well-documented pathogenic variants in both somatic and germline contexts. The RASopathy VCEP assigns PM5 at Moderate strength when one [likely] pathogenic residue change exists at the same codon. Details ▾Hide ▴
Evidence considered
- Multiple pathogenic missense changes at NRAS codon 12 are well-established (G12D
- G12V
- G12S
- G12A
- G12R).
- PM5 candidate search identified the variant as a same-residue missense but automated comparator retrieval returned no candidates.
- Codon 12 is a well-known oncogenic hotspot across all RAS genes.
Still missing
- Automated PM5 candidate retrieval returned no candidates
- manual confirmation of G12 pathogenic comparators relied on established clinical knowledge.
Sources
PP3 SupportingThe REVEL score for this missense variant is 0.773, which meets the RASopathy VCEP threshold of ≥0.7 for PP3 at Supporting strength. SpliceAI predicts no splice impact (max delta = 0.00), consistent with a missense effect. Details ▾Hide ▴
Evidence considered
- REVEL score = 0.773 (≥0.7 VCEP threshold).
- SpliceAI max delta score = 0.00 (no predicted splice impact).
Sources
Not met · 3 · evaluated, threshold not reached
BA1 The variant is absent from gnomAD. The RASopathy VCEP BA1 threshold requires a gnomAD filtering allele frequency ≥0.05%, which is not met. Details ▾Hide ▴
Evidence considered
- Variant is absent from gnomAD v2.1 and v4.1
- allele frequency = 0.
Sources
BS1 The variant is absent from gnomAD. The RASopathy VCEP BS1 threshold requires a gnomAD filtering allele frequency ≥0.025%, which is not met. Details ▾Hide ▴
Evidence considered
- Variant is absent from gnomAD v2.1 and v4.1
- allele frequency = 0.
Sources
BP4 The REVEL score for this missense variant is 0.773, which exceeds the RASopathy VCEP BP4 threshold of ≤0.3. Multiple lines of computational evidence suggest a deleterious effect, and BP4 is not met. Details ▾Hide ▴
Evidence considered
- REVEL = 0.773 (>0.3 threshold for BP4).
- BayesDel = 0.298187.
- SpliceAI max delta = 0.00 (no splice impact).
Sources
Not assessed · 9 · no assessment recorded
PS2 No de novo occurrence data for NRAS G12C in a patient with a RASopathy phenotype was identified in any reviewed publication. De novo evidence with confirmed parentage is required to apply this criterion under the RASopathy VCEP. Details ▾Hide ▴
Still missing
- No de novo case reports or family studies with confirmed parentage for this variant were available for review.
PS3 No functional assay data from VCEP-approved assay platforms (RAS Activation, MEK Activation, ERK Activation) were identified for NRAS G12C in the reviewed publications. The VCEP-approved functional studies for NRAS cite PMIDs 19966803, 28594414, and 21263000, none of which were available for full-text review in this case. OncoKB notes Likely Gain-of-function based on curated somatic literature, but this does not independently satisfy the VCEP functional assay requirements for germline PS3 application. Details ▾Hide ▴
Evidence considered
- OncoKB classifies NRAS G12C as Likely Oncogenic / Likely Gain-of-function based on somatic cancer literature.
- VCEP-approved functional assay PMIDs for NRAS (19966803
- 28594414
- 21263000) were not available for review.
Still missing
- No VCEP-approved functional assay data (RAS Activation
- MEK Activation
- or ERK Activation) for this specific variant was available.
- VCEP-approved NRAS functional study PMIDs (19966803
- 28594414
- 21263000) were not retrieved for full-text review.
Sources
oncokb ↗vcep_svi_rasopathy_vcep_v2_approved_functional_studies
PS4 No proband count data specific to NRAS G12C in a RASopathy/germline context was identified in the reviewed publications. The VCEP PS4 criterion requires point-based scoring based on proband counts with RASopathy phenotypes, but no such counts were extractable from the available evidence. Somatic observations (COSMIC n=273; 1 colorectal cancer patient in PMID 33637626) are not directly applicable to germline PS4. Details ▾Hide ▴
Evidence considered
- COSMIC reports NRAS G12C in 273 somatic cancer samples.
- PMID 33637626 reports 1 NRAS G12C patient in a somatic NCI-MATCH trial (colorectal cancer).
Still missing
- No germline/RASopathy proband counts available for review.
- ClinVar submissions (2 clinical labs) do not disclose proband counts.
PM6 No assumed de novo data without confirmation of parentage was identified for this variant in any reviewed publication. The RASopathy VCEP applies point-based scoring for PM6 but requires case-level data that was not available. Details ▾Hide ▴
Still missing
- No de novo case reports or assumed de novo observations for this variant were available for review.
PP1 No cosegregation data was identified for this variant. The RASopathy VCEP requires ≥3 informative meioses for Supporting, ≥5 for Moderate, and ≥7 for Strong. No family studies were available for review. Details ▾Hide ▴
Still missing
- No family cosegregation studies for this variant were available for review.
BS2 No data on healthy adult individuals carrying NRAS G12C was identified. The RASopathy VCEP requires observation in healthy homozygote/heterozygote individuals for BS2 application. Details ▾Hide ▴
Still missing
- No healthy control or unaffected individual data for this variant was available.
BS4 No lack-of-segregation data was identified for this variant. The RASopathy VCEP requires only one informative meiosis for BS4 at Strong, but no family studies were available for review. Details ▾Hide ▴
Still missing
- No family segregation studies for this variant were available.
BP2 No data on an alternative molecular cause of a RASopathy in the same gene or in cis/trans with a pathogenic variant was identified for this case. Details ▾Hide ▴
Still missing
- No data on alternative molecular causes or phase with other variants.
BP5 No data on an alternative molecular cause of disease in a different gene was identified for this case. Details ▾Hide ▴
Still missing
- No data on alternative molecular diagnoses in a different gene.
Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 VCEPPVS1 is not applicable for NRAS under the RASopathy VCEP v2.3.0. This is a missense variant (c.34G>T, p.Gly12Cys) and does not fall into null-variant buckets (nonsense, frameshift, canonical splice). The VCEP explicitly marks PVS1 as Not Applicable for this gene. Details ▾Hide ▴
Evidence considered
- CSPEC/VCEP RASopathy v2.3.0 specifies PVS1 as Not Applicable for NRAS
- the variant is a missense substitution
- not a null variant.
Sources
PM3 VCEPPM3 applies to recessive disorders with a variant detected in trans with a pathogenic variant. RASopathies are autosomal dominant, and the VCEP specifies PM3 as Not Applicable. Details ▾Hide ▴
PM4 N/APM4 applies to protein length changes from in-frame deletions/insertions or stop-loss variants. This is a missense substitution and does not alter protein length. Details ▾Hide ▴
Evidence considered
- Missense substitution
- PM4 applies only to in-frame indels or stop-loss variants.
Sources
PP2 VCEPThe RASopathy VCEP v2.3.0 specifies PP2 as Not Applicable because the missense Z-score for NRAS is <3.09 in gnomAD. Details ▾Hide ▴
Evidence considered
- VCEP declares PP2 not applicable for NRAS (missense Z-score <3.09).
Sources
PP4 VCEPThe RASopathy VCEP v2.3.0 specifies PP4 as Not Applicable; phenotype specificity is assessed through PS4 instead. Details ▾Hide ▴
PP5 VCEPThe RASopathy VCEP v2.3.0 specifies PP5 as Not Applicable for this VCEP, consistent with ClinGen SVI VCEP Review Committee recommendations. Details ▾Hide ▴
Evidence considered
- VCEP declares PP5 not for use as recommended by ClinGen SVI VCEP Review Committee.
Sources
BS3 VCEPThe RASopathy VCEP v2.3.0 specifies BS3 as Not Applicable for this gene. Details ▾Hide ▴
BP1 N/ABP1 under the RASopathy VCEP applies only to truncating variants (nonsense, frameshift, canonical splice site, initiation codon, whole gene or multi-exon deletion) in genes where the disease mechanism is gain-of-function. This variant is a missense substitution (c.34G>T, p.Gly12Cys) and does not qualify. Details ▾Hide ▴
Evidence considered
- Missense variant does not meet VCEP criteria for BP1 (truncating variants only).
Sources
BP3 VCEPBP3 applies to in-frame deletions/insertions in repetitive regions. This is a substitution variant and the RASopathy VCEP specifies no known benign repetitive areas in RASopathy genes. Details ▾Hide ▴
Evidence considered
- Missense substitution
- BP3 not applicable per VCEP (no known benign repetitive regions in RASopathy genes).
Sources
BP6 VCEPThe RASopathy VCEP v2.3.0 specifies BP6 as Not Applicable for this VCEP, consistent with ClinGen SVI VCEP Review Committee recommendations. Details ▾Hide ▴
Evidence considered
- VCEP declares BP6 not for use as recommended by ClinGen SVI VCEP Review Committee.
Sources
BP7 N/ABP7 applies only to synonymous (silent) variants for which splicing prediction algorithms predict no impact. This variant is a missense substitution (c.34G>T, p.Gly12Cys) and does not qualify. Details ▾Hide ▴
Evidence considered
- Missense variant does not meet VCEP criteria for BP7 (synonymous variants only).
Sources
PS5 N/APS5 is not defined in the ClinGen RASopathy Expert Panel Specifications for NRAS Version 2.3.0. This criterion is not part of the VCEP framework for this gene. Details ▾Hide ▴
Evidence considered
- Criterion not specified in the NRAS RASopathy VCEP v2.3.0 criteria set.
Sources
Identifiers
- Gene
- NRAS
- Transcript
- NM_002524.4
- Coding (HGVS c.)
- NM_002524.4:c.34G>T
- Protein (HGVS p.)
- NP_002515.1:p.(Gly12Cys)
- GRCh38
- chr1:114716127 C>A
- GRCh37
- chr1:115258748 C>A
- ClinVar
- 40468
- COSMIC
- COSV54736487
Gene diagram
Every interpreted variant in NRAS, mapped onto the exon structure of NM_002524.4. Select a row to find it on the plot.
NRASNM_002524.4
Fetching transcript structure from UCSC…
Exons
—
Transcript span
—
Strand
—
Variants mapped
—
Source
UCSC ncbiRefSeqCurated
All variants in NRAS
—
Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.773
- BayesDel
- 0.298
How the predictions were used
PP3 SupportingThe REVEL score for this missense variant is 0.773, which meets the RASopathy VCEP threshold of ≥0.7 for PP3 at Supporting strength. SpliceAI predicts no splice impact (max delta = 0.00), consistent with a missense effect. Details ▾Hide ▴
Evidence considered
- REVEL score = 0.773 (≥0.7 VCEP threshold).
- SpliceAI max delta score = 0.00 (no predicted splice impact).
Sources
BP4 The REVEL score for this missense variant is 0.773, which exceeds the RASopathy VCEP BP4 threshold of ≤0.3. Multiple lines of computational evidence suggest a deleterious effect, and BP4 is not met. Details ▾Hide ▴
Evidence considered
- REVEL = 0.773 (>0.3 threshold for BP4).
- BayesDel = 0.298187.
- SpliceAI max delta = 0.00 (no splice impact).
Sources
BP7 N/ABP7 applies only to synonymous (silent) variants for which splicing prediction algorithms predict no impact. This variant is a missense substitution (c.34G>T, p.Gly12Cys) and does not qualify. Details ▾Hide ▴
Evidence considered
- Missense variant does not meet VCEP criteria for BP7 (synonymous variants only).
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.773. BayesDel score = 0.298187.
8 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Recorded publications
-
PMID 26619011 ↗Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.Pan-cancer analysis of 11,119 tumors identifying 470 mutational hotspots across 275 genes. NRAS is discussed as a gene with tumor-specific mutational hotspots, but the specific NRAS G12C variant is not identified or discussed in this paper.Does not name this variant
-
PMID 28572459 ↗AACR Project GENIE: Powering Precision Medicine through an International Consortium.Describes the AACR Project GENIE consortium for sharing clinical-grade cancer genomic data. Provides high-level analysis of ~19,000 samples but does not identify or discuss the specific NRAS G12C variant.Does not name this variant
-
PMID 33637626 ↗Differential Outcomes in Codon 12/13 and Codon 61 NRAS-Mutated Cancers in the Phase II NCI-MATCH Trial of Binimetinib in Patients with NRAS-Mutated Tumors.Phase II NCI-MATCH trial of binimetinib in NRAS-mutated cancers. Table 2 reports one colorectal cancer patient with NRAS Gly12Cys (1/24 colorectal, 4.2%). The paper notes NRAS G12C was present in 1 of 17 (5.8%) codon 12-mutated tumors overall. The study context is somatic cancer, not germline RASopathy.Names this variant
Quoted passage
NRAS G12C mutations were present in 1 of 17 (5.8%) codon 12-mutated tumors and 2 of 8 (25%) codon 13-mutated tumors.
Table 2; Discussion paragraph regarding NRAS G12C/G13C-targeted therapies
-
PMID 9219684 ↗The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants.Crystal structure of the H-Ras–RasGAP complex at 2.5 Å resolution. Discusses the structural role of glycine-12 in GTP hydrolysis and how mutations at this position (including G12A modeled in silico) would sterically interfere with the transition state. NRAS is not specifically discussed; the study uses H-Ras.Does not name this variant
Quoted passage
Glycine-12 in the transition state mimic is within van der Waals distance of both arginine-789 of GAP-334 and glutamine-61 of Ras, and even its mutation to alanine would disturb the arrangements of residues in the transition state.
Abstract; Figure 4C; Discussion
-
PMID 26037647 ↗Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations.Hunter JC et al. · 2015Biochemical and structural analysis of common cancer-associated KRAS mutations (G12A, G12C, G12D, G12R, G12V, G13D, Q61L, Q61H). KRAS G12C is characterized for nucleotide exchange kinetics, intrinsic and GAP-stimulated GTPase activity, and RAF kinase affinity. NRAS is mentioned only in passing; all experimental data pertain to KRAS, not NRAS.Does not name this variant
Quoted passage
The G12C mutation had minimal impact on the intrinsic hydrolysis rate.
Throughout (KRAS G12C is a primary subject of the paper)
-
PMID 6092966 ↗Biological properties of human c-Ha-ras1 genes mutated at codon 12.Seeburg PH et al. · 1984No paper-specific finding is recorded.
-
PMID 19681119 ↗RAS signaling dysregulation in human embryonal Rhabdomyosarcoma.Martinelli S et al. · 2009Investigated NRAS mutations in 31 primary embryonal rhabdomyosarcoma tumors. Identified NRAS mutations in 20% of cases, all at codon 61 (Q61K, Q61R) and in cell lines (Q61H, Q61L). No codon 12 mutations were identified, and NRAS G12C was not observed in this cohort.Does not name this variant
Quoted passage
All mutations were missense changes, affected the glutamine residue at codon 61, and introduced a positively charged amino acid residue.
Results; Table 1
-
PMID 20963938 ↗CEBPA-Associated Familial Acute Myeloid Leukemia (AML).Review of CEBPA-associated familial acute myeloid leukemia. Does not discuss NRAS mutations or the G12C variant.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
2 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/643243109
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/40468/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/1-115258748-C-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr1-114716127-C-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/1-114716127-C-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_002524.4%3Ac.34G%…
- OncoKB ↗www.oncokb.org/gene/NRAS/G12C
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=136034268
- 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 Pathogenic (2 clinical laboratories). (ClinVarID = 40468)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.773. BayesDel score = 0.298187.
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 lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV54736487, n = 273 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.