About NRAS
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
NRAS c.183A>C, p.(Gln61His)
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 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: 4
Benign evidence criteria: 0
Pathogenic criteria applied · 4
PM1Moderate
PM1 · moderate
Gln61 (amino acid position 61) lies within the Switch II (SW2) functional domain (AA 57-64), one of four critical and well-established functional domains defined by the RASopathy VCEP (P-loop AA 10-17, SW1 AA 25-40, SW2 AA 57-64, SAK AA 145-156). SW2 is essential for GTP hydrolysis and effector interaction. Per VCEP, PM1 is applicable at moderate strength for variants in these domains.
PM2Supporting
PM2 · supporting
NM_002524.5:c.183A>C is absent from all population databases: gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0. Per VCEP RASopathy specifications, PM2 is applied at supporting strength when the variant is absent from gnomAD controls.
PM5Moderate
PM5 · moderate
Codon 61 in NRAS harbors multiple well-established pathogenic missense variants (Q61R, Q61K, Q61L) reported in ClinVar and the literature. Per VCEP, one [likely] pathogenic residue change at the same codon qualifies for PM5 at moderate strength. The PM5 pipeline did not collect proband counts to support PM5_Strong (≥2 different LP/P residue changes at same codon observed in ≥5 probands), though multiple Q61 variants are established as pathogenic in the literature.
PP3Supporting
PP3 · supporting
REVEL score for NM_002524.5:c.183A>C (p.Q61H) is 0.742, which meets the VCEP threshold of REVEL ≥ 0.7 for PP3 at supporting strength. SpliceAI predicts no significant splice impact (max delta score = 0.00), consistent with a missense effect predicted to be deleterious.
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 NRAS Version 2.3.0 v2.3.0 criteria-combination framework: matched Rule14 (2 Pathogenic.Moderate + Pathogenic.Supporting >=2) with applied criteria: PM1 moderate, PM2 supporting, PM5 moderate, PP3 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.
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
Not recorded
A ClinVar laboratory submission summary was not recorded. 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: Gain-of-function; curated oncogenicity label: Oncogenic.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
149 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV54736320, n = 149 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.
25 criteria with recorded statuses: 4 met · 12 not met · 1 not assessed · 8 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_002524.5:c.183A>C (p.Gln61His) is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases (PM2_Supporting per VCEP).
Gln61 lies within the Switch II functional domain (AA 57-64), a critical and well-established functional domain defined by the RASopathy VCEP for GTP hydrolysis and effector interaction (PM1_Moderate per VCEP).
Multiple established pathogenic missense variants exist at the same codon (Q61R, Q61K, Q61L) in NRAS, satisfying PM5 at moderate strength per VCEP specifications.
REVEL in silico score of 0.742 meets the VCEP threshold for PP3 at supporting strength, predicting a deleterious amino acid substitution.
NM_002524.5:c.183A>C has been reported in ClinVar as Tier I - Strong (ClinVar ID 4530443) and classified as Oncogenic by OncoKB with gain-of-function mechanism. The variant is recurrent in somatic cancers (COSMIC n=149).
No VCEP-approved functional assay data, de novo observations, case-control studies, or segregation data are available for this variant in the germline RASopathy context.
No criteria match.
Met · 4
PM1 ModerateGln61 (amino acid position 61) lies within the Switch II (SW2) functional domain (AA 57-64), one of four critical and well-established functional domains defined by the RASopathy VCEP (P-loop AA 10-17, SW1 AA 25-40, SW2 AA 57-64, SAK AA 145-156). SW2 is essential for GTP hydrolysis and effector interaction. Per VCEP, PM1 is applicable at moderate strength for variants in these domains. Details ▾Hide ▴
Evidence considered
- CSPEC VCEP v2.3.0: PM1 moderate applicable to critical functional domains SW2 (AA 57-64)
- Gln61 is a catalytic residue in the Ras GTPase active site within SW2
- Structure/function papers confirm Q61 is critical for GTP hydrolysis
- Residue lies in a statistically significant hotspot (cancerhotspots.org)
- OncoKB: Q61H classified as Oncogenic
- gain-of-function
Sources
PM2 SupportingNM_002524.5:c.183A>C is absent from all population databases: gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0. Per VCEP RASopathy specifications, 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)
- Absent from gnomAD-Canada v1.0 (genomes)
- CSPEC VCEP v2.3.0: PM2_Supporting when absent from gnomAD
Sources
PM5 ModerateCodon 61 in NRAS harbors multiple well-established pathogenic missense variants (Q61R, Q61K, Q61L) reported in ClinVar and the literature. Per VCEP, one [likely] pathogenic residue change at the same codon qualifies for PM5 at moderate strength. The PM5 pipeline did not collect proband counts to support PM5_Strong (≥2 different LP/P residue changes at same codon observed in ≥5 probands), though multiple Q61 variants are established as pathogenic in the literature. Details ▾Hide ▴
Evidence considered
- CSPEC VCEP v2.3.0: PM5_Moderate with 1 LP/P residue change at same codon
- Q61R
- Q61K
- Q61L are established pathogenic variants in NRAS at same codon
- COSMIC confirms multiple different amino acid substitutions at codon 61 across cancer samples
Still missing
- PM5 pipeline did not collect proband counts
- expert review needed to determine whether ≥5 probands with other Q61 codon LP/P variants supports PM5_Strong
Sources
PP3 SupportingREVEL score for NM_002524.5:c.183A>C (p.Q61H) is 0.742, which meets the VCEP threshold of REVEL ≥ 0.7 for PP3 at supporting strength. SpliceAI predicts no significant splice impact (max delta score = 0.00), consistent with a missense effect predicted to be deleterious. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.742 (≥0.7 threshold per VCEP)
- SpliceAI max delta: 0.00 (no confounding splice effect)
- CSPEC VCEP v2.3.0: PP3_Supporting when REVEL ≥ 0.7 for missense variants
Sources
Not met · 12 · evaluated, threshold not reached
PS2 No de novo observation data available for NM_002524.5:c.183A>C in a RASopathy proband. ClinVar submissions provide no usable de novo reports. Details ▾Hide ▴
Evidence considered
- ClinVar: 0 usable submissions
- no de novo reports
Still missing
- No de novo observations identified for this variant
Sources
PS3 No VCEP-approved functional assay has directly tested NM_002524.5:c.183A>C (p.Q61H). The VCEP-approved functional studies for NRAS (RAS Activation Assay, MEK Activation Assay, ERK Activation Assay, AKT Phosphorylation Assay) list validation controls that do not include Q61H (validation controls: G12V, I24N, T58I, G60E). While NRAS Q61H has been studied in the RD rhabdomyosarcoma cell line context (PMID:23103856), this is a somatic cancer model using an endogenous mutation, not a directed functional assay of the variant meeting VCEP standards for clinical germline interpretation. Details ▾Hide ▴
Evidence considered
- VCEP-approved NRAS functional assays: each provides PS3_Supporting per VCEP when variant tested
- Q61H not among validation controls in approved NRAS functional study publications
- PMID:23103856 describes NRAS Q61H signaling in RD rhabdomyosarcoma cell line but this is not a VCEP-approved functional assay
Still missing
- No VCEP-approved functional assay data for Q61H specifically
- VCEP-approved assay PMIDs for NRAS (19966803
- 28594414
- 21263000) not available in case folder
- could not verify whether Q61H was among tested variants
Sources
PS4 No proband counts available for NM_002524.5:c.183A>C in the RASopathy clinical context. ClinVar submissions total 0 usable for classification. No case-control or cohort data meeting VCEP PS4 point criteria were identified. Details ▾Hide ▴
Evidence considered
- ClinVar: 0 submissions usable for classification
- no proband counts
Still missing
- No proband-level data identified
- Somatic observations in cancer cohorts (COSMIC n=149
- multiple publications) do not satisfy germline PS4
Sources
PM6 No de novo observation data available for NM_002524.5:c.183A>C. Per VCEP, PM6 uses point-based scoring (0.5-2 points) requiring confirmed de novo status. No de novo events were identified in ClinVar submissions or literature. Details ▾Hide ▴
Evidence considered
- ClinVar: 0 usable submissions
- no de novo reports identified
Still missing
- No de novo observations available
Sources
PP1 No co-segregation data available for NM_002524.5:c.183A>C. Per VCEP, PP1 requires ≥3 informative meioses for supporting, ≥5 for moderate, and ≥7 for strong. No family studies were identified. Details ▾Hide ▴
Evidence considered
- No segregation data identified in ClinVar or literature
Still missing
- No family segregation studies available
BA1 NM_002524.5:c.183A>C is absent from gnomAD (allele frequency = 0). The VCEP BA1 threshold is gnomAD filtering allele frequency ≥ 0.05%. This variant does not meet the BA1 threshold. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1
- v4.1
- and Canada
- CSPEC VCEP v2.3.0: BA1 requires AF ≥ 0.05%
Sources
BS1 NM_002524.5:c.183A>C is absent from gnomAD (allele frequency = 0). The VCEP BS1 threshold is gnomAD filtering allele frequency ≥ 0.025%. This variant does not meet the BS1 threshold. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1
- v4.1
- and Canada
- CSPEC VCEP v2.3.0: BS1 requires AF ≥ 0.025%
Sources
BS2 No observations of NM_002524.5:c.183A>C in healthy adult individuals. Variant is absent from gnomAD, which precludes evidence of presence in unaffected controls. Per VCEP point-based scoring, no points can be assigned for BS2. Details ▾Hide ▴
Evidence considered
- Absent from all population databases — no healthy heterozygous or homozygous individuals identified
- CSPEC VCEP v2.3.0: BS2 requires point-based scoring from healthy individual observations
Still missing
- No healthy individual observations available
Sources
BS4 No segregation data demonstrating lack of co-segregation with a RASopathy phenotype. Per VCEP, BS4 requires only one informative meiosis showing non-segregation. No family studies were identified. Details ▾Hide ▴
Evidence considered
- No family segregation data available
Still missing
- No family studies identified
BP2 No evidence of an alternative molecular cause of a RASopathy in the same gene, and no cis/trans phase data available. Per VCEP, BP2 requires point-based scoring for an alternative molecular cause. No data meet any point threshold. Details ▾Hide ▴
Evidence considered
- No alternative molecular cause or phase data identified
Still missing
- No in trans or in cis observations available
BP4 REVEL score for NM_002524.5:c.183A>C is 0.742, which exceeds the VCEP BP4 threshold of REVEL ≤ 0.3. The in silico prediction does not support a benign interpretation. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.742 (BP4 requires ≤0.3 per VCEP)
- SpliceAI max delta: 0.00
Sources
BP5 No evidence of an alternative molecular cause for a RASopathy in a different gene. Per VCEP, BP5 requires point-based scoring for alternative molecular causes. No data available. Details ▾Hide ▴
Evidence considered
- No alternative molecular cause identified
Still missing
- No data on alternative molecular diagnoses
Not assessed · 1 · no assessment recorded
PS1 PS1 per VCEP applies when the same amino acid change has been previously established as pathogenic regardless of nucleotide change across HRAS, KRAS, MRAS, NRAS, RIT1, and RRAS2. Q61H (p.Gln61His) is a well-established pathogenic variant in HRAS (Costello syndrome) and KRAS. However, the variant NM_002524.5:c.183A>C (p.Q61H) is itself the canonical change being assessed in this case. Whether PS1 can be applied when the variant under assessment produces the same amino acid change as a previously classified pathogenic variant at the same residue in a paralogous gene requires expert adjudication. Details ▾Hide ▴
Evidence considered
- CSPEC VCEP v2.3.0 PS1 rule: same amino acid change as previously established pathogenic regardless of nucleotide change
- applicable across RAS paralogs
- OncoKB: Q61H classified as Oncogenic
- gain-of-function
Still missing
- Requires expert determination whether Q61H in a paralogous RAS gene (HRAS/KRAS) satisfies PS1 for NRAS Q61H
- or whether this would constitute double-counting with the variant's own pathogenicity
Sources
Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 VCEPCSPEC RASopathy VCEP v2.3.0 marks PVS1 as not applicable for NRAS. Additionally, NM_002524.5:c.183A>C is a missense substitution and does not fall into null-variant buckets (nonsense, frameshift, canonical splice). Details ▾Hide ▴
Evidence considered
- CSPEC RASopathy VCEP v2.3.0 criterion applicability: Not Applicable
Sources
PP2 VCEPVCEP RASopathy specifications mark PP2 as not applicable because the missense z-score for NRAS is <3.09 in gnomAD. Details ▾Hide ▴
PP4 VCEPVCEP RASopathy specifications mark PP4 as not applicable; phenotype specificity is addressed under PS4 instead. Details ▾Hide ▴
PP5 VCEPVCEP specifications mark PP5 as not applicable per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation. Details ▾Hide ▴
Evidence considered
- CSPEC VCEP v2.3.0: PP5 not applicable per ClinGen SVI VCEP Review Committee
Sources
BS3 VCEPVCEP RASopathy specifications mark BS3 as not applicable. Details ▾Hide ▴
BP1 N/AVCEP BP1 applies only to truncating variants (nonsense, frameshift, canonical splice site, initiation codon, entire gene or multi-exon deletion) in genes where disease mechanism is gain-of-function. NM_002524.5:c.183A>C is a missense substitution, not a truncating variant. Details ▾Hide ▴
Evidence considered
- CSPEC VCEP v2.3.0: BP1 restricted to truncating LOF variants
- this is a missense substitution
Sources
BP6 VCEPVCEP specifications mark BP6 as not applicable per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation. Details ▾Hide ▴
Evidence considered
- CSPEC VCEP v2.3.0: BP6 not applicable per ClinGen SVI VCEP Review Committee
Sources
BP7 N/AVCEP BP7 applies only to synonymous (silent) variants or intronic positions outside canonical splice sites, in conjunction with BP4. NM_002524.5:c.183A>C is a missense substitution producing p.Gln61His and does not qualify. Details ▾Hide ▴
Evidence considered
- CSPEC VCEP v2.3.0: BP7 applicable to synonymous/intronic variants only
- this is missense
Sources
Identifiers
- Gene
- NRAS
- Transcript
- NM_002524.5
- Coding (HGVS c.)
- NM_002524.5:c.183A>C
- Protein (HGVS p.)
- NP_002515.1:p.(Gln61His)
- GRCh38
- chr1:114713907 T>G
- GRCh37
- chr1:115256528 T>G
- ClinVar
- 4530443
- COSMIC
- COSV54736320
Gene diagram
Every interpreted variant in NRAS, mapped onto the exon structure of NM_002524.5. Select a row to find it on the plot.
NRASNM_002524.5
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 NRAS
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.742
- BayesDel
- 0.130
How the predictions were used
PP3 SupportingREVEL score for NM_002524.5:c.183A>C (p.Q61H) is 0.742, which meets the VCEP threshold of REVEL ≥ 0.7 for PP3 at supporting strength. SpliceAI predicts no significant splice impact (max delta score = 0.00), consistent with a missense effect predicted to be deleterious. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.742 (≥0.7 threshold per VCEP)
- SpliceAI max delta: 0.00 (no confounding splice effect)
- CSPEC VCEP v2.3.0: PP3_Supporting when REVEL ≥ 0.7 for missense variants
Sources
BP4 REVEL score for NM_002524.5:c.183A>C is 0.742, which exceeds the VCEP BP4 threshold of REVEL ≤ 0.3. The in silico prediction does not support a benign interpretation. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.742 (BP4 requires ≤0.3 per VCEP)
- SpliceAI max delta: 0.00
Sources
BP7 N/AVCEP BP7 applies only to synonymous (silent) variants or intronic positions outside canonical splice sites, in conjunction with BP4. NM_002524.5:c.183A>C is a missense substitution producing p.Gln61His and does not qualify. Details ▾Hide ▴
Evidence considered
- CSPEC VCEP v2.3.0: BP7 applicable to synonymous/intronic variants only
- this is missense
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.742. BayesDel score = 0.130143.
6 paper records listed. 2 cited in the classification.
Cited in the classification
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PMID 10574788 ↗The pre-hydrolysis state of p21(ras) in complex with GTP: new insights into the role of water molecules in the GTP hydrolysis reaction of ras-like proteins.Scheidig AJ et al. · 1999 Nov 15High-resolution crystal structure of p21ras (H-Ras) in complex with GTP using freeze-trapping, elucidating the role of Gln61 in intrinsic GTP hydrolysis. Demonstrates Gln61 positions the catalytic water molecule. NM_002524.5:c.183A>C (NRAS Q61H) was not identified in this paper.→ PM1 Does not name this variant
Source detail
The results shed light on the function of Gln61 in the intrinsic GTP hydrolysis reaction.
Location Throughout; Gln61 discussed as catalytic residue in switch II region
Context X-ray crystallography of H-Ras with caged GTP photolysis and rapid freeze-trapping at 100K
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PMID 20194776 ↗Allosteric modulation of Ras positions Q61 for a direct role in catalysis.Buhrman G et al. · 2010 Mar 16Structural biology study of H-Ras demonstrating the catalytic role of Gln61 in intrinsic GTP hydrolysis via an allosteric switch mechanism. Discusses RasQ61L oncogenic mutant in structural context. NM_002524.5:c.183A>C (NRAS Q61H) was not identified in this paper.→ PM1 Does not name this variant
Source detail
Mutants of residue Q61 impair the GTPase activity of Ras and are found prominently in human cancers.
Location Throughout; Q61 discussed in context of catalytic mechanism
Context X-ray crystallography of H-Ras GppNHp and GTP complexes, allosteric calcium acetate binding studies
Other recorded publications
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PMID 23103856 ↗Oncogenic and wild-type Ras play divergent roles in the regulation of mitogen-activated protein kinase signaling.Young A et al. · 2013NRAS Q61H studied in the RD rhabdomyosarcoma cell line as a model of oncogenic Ras signaling. Depletion of oncogenic NRAS Q61H reduced basal ERK phosphorylation, while wild-type Ras isoforms mediated EGF-induced MAPK signaling in the same cells. Demonstrates NRAS Q61H drives constitutive MAPK pathway activation in a somatic cancer context.Names this variant
Quoted passage
the RD rhabdomyosarcoma cell line (NRAS Q61H; Catalog of Somatic Mutations in Cancer, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom)
Introduction para 3; Results; Figures 1-3
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PMID 25148578 ↗Beyond BRAF(V600): clinical mutation panel testing by next-generation sequencing in advanced melanoma.Clinical NGS panel testing of 699 advanced melanoma patients for hotspot mutations in 46 genes including NRAS. Reports frequency and patterns of NRAS mutations in melanoma. NM_002524.5:c.183A>C (NRAS Q61H) was not specifically identified in the accessible portion of the full text.Does not name this variant
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PMID 26090869 ↗Molecular spectrum of BRAF, NRAS and KRAS gene mutations in plasma cell dyscrasias: implication for MEK-ERK pathway activation.Targeted NGS study of BRAF, NRAS, and KRAS mutations in 167 plasma cell dyscrasia patients (MM, pPCL, sPCL). NRAS Q61H identified in multiple myeloma patients with varying variant allele frequencies (VAF 6-41%). Sequential analysis showed NRAS Q61H emerging or expanding at relapse in several cases, indicating clonal selection.Names this variant
Quoted passage
the loss of KRAS G12V in MM-146, which showed a concurrent increase in the allele frequency of NRAS Q61H from 8% to 41%
Table 2 (sequential analysis); Results section 'NRAS and KRAS mutations'
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PMID 34166060 ↗Genomic Classification and Clinical Outcome in Rhabdomyosarcoma: A Report From an International Consortium.International consortium study of driver mutations in rhabdomyosarcoma. Reports genomic classification and clinical outcomes. NM_002524.5:c.183A>C (NRAS Q61H) was not identified in the accessible full text.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
Captured ClinVar source record
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/4530443/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/1-115256528-T-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr1-114713907-T-G?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/1-114713907-T-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_002524.5%3Ac.183A…
- OncoKB ↗www.oncokb.org/gene/NRAS/Q61H
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=136034147
- 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 but submission details could not be extracted. (ClinVarID = 4530443)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.742. BayesDel score = 0.130143.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Gain-of-function; curated oncogenicity label: Oncogenic.
Somatic
This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV54736320, n = 149 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.