HRASc.182A>GPathogenic

Print report

Variant interpretation report

HRAS c.182A>G, p.(Gln61Arg)

NM_005343.4:c.182A>G NP_005334.1:p.(Gln61Arg) View identifiers

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.

About HRAS

No gene-level summary was recorded for this case.

Key facts

Condition: RASopathy
Inheritance: Autosomal dominant
Evidence used: 1 strong (pathogenic) · 2 moderate (pathogenic) · 2 supporting (pathogenic)
Expert rules: ClinGen HRAS VCEP v2.3.0
Other laboratories (ClinVar): 3 Likely pathogenic · 1 Pathogenic
Pipeline record: 17 Jul 2026 · version 7.0.4

Evidence considered

View criteria

Applied evidence criteria

PS1 (strong): The p.Gln61Arg substitution is a previously established pathogenic variant at the analogous residue in KRAS and NRAS. Per the RASopathy VCEP, PS1 is applicable for observed analogous residue positions across HRAS, KRAS, MRAS, NRAS, RIT1, and RRAS2. Q61R in KRAS and NRAS is a well-established oncogenic gain-of-function mutation catalogued in COSMIC and ClinVar.
PM1 (moderate): The variant substitutes Gln61Arg within the Switch II (SW2) domain (HRAS amino acids 57-64), a critical and well-established functional domain defined by the RASopathy VCEP. SW2 is essential for GTP hydrolysis and GAP interaction. Residue Q61 is a known cancer hotspot (cancerhotspots.org) and is recurrently mutated in somatic cancers (COSMIC n=417). No benign variation is observed at this residue.
PM2 (supporting): The variant is absent from gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (genomes), meeting the VCEP requirement for absence from population controls.
PM5 (moderate): At least one other pathogenic missense change has been established at codon 61 of HRAS. The RASopathy VCEP recognizes Q61L (c.182A>T) and Q61K as pathogenic/likely pathogenic changes at the same codon, satisfying the requirement for one (likely) pathogenic residue change at the same codon.
PP3 (supporting): REVEL score of 0.811 meets the VCEP threshold of ≥0.7 for pathogenic computational evidence. SpliceAI predicts no splice impact (max delta score = 0.00), consistent with a missense effect rather than a splicing defect. The disease mechanism (gain-of-function) is consistent with a missense change.

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 HRAS 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 p.Gln61Arg substitution is a previously established pathogenic variant at the analogous residue in KRAS and NRAS. Per the RASopathy VCEP, PS1 is applicable for observed analogous residue positions across HRAS, KRAS, MRAS, NRAS, RIT1, and RRAS2. Q61R in KRAS and NRAS is a well-established oncogenic gain-of-function mutation catalogued in COSMIC and ClinVar.

PM1Moderate

PM1 · moderate

The variant substitutes Gln61Arg within the Switch II (SW2) domain (HRAS amino acids 57-64), a critical and well-established functional domain defined by the RASopathy VCEP. SW2 is essential for GTP hydrolysis and GAP interaction. Residue Q61 is a known cancer hotspot (cancerhotspots.org) and is recurrently mutated in somatic cancers (COSMIC n=417). No benign variation is observed at this residue.

PM2Supporting

PM2 · supporting

The variant is absent from gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (genomes), meeting the VCEP requirement for absence from population controls.

PM5Moderate

PM5 · moderate

At least one other pathogenic missense change has been established at codon 61 of HRAS. The RASopathy VCEP recognizes Q61L (c.182A>T) and Q61K as pathogenic/likely pathogenic changes at the same codon, satisfying the requirement for one (likely) pathogenic residue change at the same codon.

PP3Supporting

PP3 · supporting

REVEL score of 0.811 meets the VCEP threshold of ≥0.7 for pathogenic computational evidence. SpliceAI predicts no splice impact (max delta score = 0.00), consistent with a missense effect rather than a splicing defect. The disease mechanism (gain-of-function) is consistent with a missense change.

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 HRAS 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.

Applied · PM2 →

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

4 reported laboratory submissions

3 Likely pathogenic · 1 Pathogenic. ClinVar API review status: criteria provided, multiple submitters, no conflicts.

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

417 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV54236691, n = 417 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under ClinGen HRAS VCEP v2.3.0, with the data and sources behind each one.

29 criteria with recorded statuses: 5 met · 11 not met · 1 not assessed · 12 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

The c.182A>G (p.Gln61Arg) missense variant in HRAS is classified as Pathogenic under the ClinGen RASopathy VCEP v2.3.0 framework.

PS1 (Strong): p.Gln61Arg is a previously established pathogenic variant at the analogous residue in KRAS and NRAS, satisfying the VCEP rule for cross-gene analogous residue application.

PM1 (Moderate): The variant falls within the Switch II domain (SW2, AA 57-64), a VCEP-defined critical functional domain essential for GTP hydrolysis and GAP interaction. Residue Q61 is a statistically significant cancer hotspot (cancerhotspots.org) with 417 somatic occurrences in COSMIC.

PM5 (Moderate): At least one other pathogenic missense change at codon 61 (e.g., Q61L) has been established in HRAS, meeting the VCEP threshold for PM5 at Moderate strength.

PM2 (Supporting): The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases, meeting the VCEP requirement for absence from controls.

PP3 (Supporting): The REVEL score of 0.811 exceeds the VCEP threshold of >=0.7 for pathogenic computational prediction. SpliceAI predicts no splice impact (max delta = 0.00).

Combination: PS1 (1 Strong) + PM1 (1 Moderate) + PM5 (1 Moderate) + PM2 (1 Supporting) + PP3 (1 Supporting) satisfies VCEP Rule 7 (1 Strong + 2 Moderate + >=2 Supporting = Pathogenic).

Met · 5

PS1 StrongThe p.Gln61Arg substitution is a previously established pathogenic variant at the analogous residue in KRAS and NRAS. Per the RASopathy VCEP, PS1 is applicable for observed analogous residue positions across HRAS, KRAS, MRAS, NRAS, RIT1, and RRAS2. Q61R in KRAS and NRAS is a well-established oncogenic gain-of-function mutation catalogued in COSMIC and ClinVar. Details ▾Hide ▴

Evidence considered

VCEP rule: same amino acid change at analogous residues in KRAS/NRAS qualifies as established pathogenic
COSMIC: codon 61 is a recurrent somatic hotspot across RAS genes
Q61R is an established activating mutation in KRAS and NRAS

Sources

cspec ↗oncokb ↗

PM1 ModerateThe variant substitutes Gln61Arg within the Switch II (SW2) domain (HRAS amino acids 57-64), a critical and well-established functional domain defined by the RASopathy VCEP. SW2 is essential for GTP hydrolysis and GAP interaction. Residue Q61 is a known cancer hotspot (cancerhotspots.org) and is recurrently mutated in somatic cancers (COSMIC n=417). No benign variation is observed at this residue. Details ▾Hide ▴

Evidence considered

VCEP-defined SW2 domain: AA 57-64
Cancer Hotspots: statistically significant residue-level hotspot
COSMIC: 417 somatic occurrences at codon 61
PMID:9219684: structural evidence that SW2/Q61 is critical for GTPase activity

Sources

cspec ↗PMID:9219684 ↗

PM2 SupportingThe variant is absent from gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (genomes), meeting the VCEP requirement for absence from population controls. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1
Absent from gnomAD v4.1
Absent from gnomAD-Canada v1.0

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PM5 ModerateAt least one other pathogenic missense change has been established at codon 61 of HRAS. The RASopathy VCEP recognizes Q61L (c.182A>T) and Q61K as pathogenic/likely pathogenic changes at the same codon, satisfying the requirement for one (likely) pathogenic residue change at the same codon. Details ▾Hide ▴

Evidence considered

VCEP PM5 rule: 1 (L)P residue change at same codon = Moderate
HRAS Q61L (c.182A>T) is a known pathogenic RASopathy variant
HRAS Q61K is an established oncogenic variant
Codon 61 is a well-characterized mutational hotspot in HRAS

Sources

cspec ↗clinvar ↗

PP3 SupportingREVEL score of 0.811 meets the VCEP threshold of ≥0.7 for pathogenic computational evidence. SpliceAI predicts no splice impact (max delta score = 0.00), consistent with a missense effect rather than a splicing defect. The disease mechanism (gain-of-function) is consistent with a missense change. Details ▾Hide ▴

Evidence considered

REVEL score: 0.811 (≥0.7 threshold)
SpliceAI max delta: 0.00 (no splice impact)

Sources

revelspliceai ↗cspec ↗

Not met · 11 · evaluated, threshold not reached

PS2 No de novo occurrence data are available for this variant. PS2 requires confirmed de novo status (both maternity and paternity confirmed) in a patient with a RASopathy phenotype and no family history. Details ▾Hide ▴

Evidence considered

No de novo case reports identified in the literature or ClinVar submissions for this variant.

Still missing

De novo data could strengthen classification if available.

PS4 No proband count data are available to meet the VCEP point-based scoring threshold. While this variant is reported in ClinVar (VCV000160364) as Likely pathogenic/Pathogenic by clinical laboratories and has been observed in somatic cancers (COSMIC, n=417), specific proband counts with RASopathy phenotypes are not available for PS4 point calculation. Details ▾Hide ▴

Evidence considered

ClinVar VCV000160364: Likely pathogenic (3 clinical labs)
Pathogenic (1 lab)
No proband-level phenotype data available for PS4 scoring

Still missing

Proband counts with RASopathy-specific phenotypes needed for PS4 point assignment.

Sources

clinvar ↗

PM6 No assumed de novo data are available for this variant. PM6 requires observation of the variant as assumed de novo (without confirmation of both maternity and paternity) in a patient with a RASopathy phenotype. Details ▾Hide ▴

Evidence considered

No assumed de novo reports identified in ClinVar or literature.

Still missing

De novo data could contribute to PM6/PS2 scoring.

PP1 No co-segregation data are available for this variant. PP1 requires observation of the variant in affected family members (≥3 informative meioses for Supporting, ≥5 for Moderate, ≥7 for Strong). Details ▾Hide ▴

Evidence considered

No segregation data identified in ClinVar submissions or literature.

Still missing

Segregation data in affected families could strengthen classification.

BA1 The variant is absent from gnomAD (filtering allele frequency = 0), which is far below the VCEP stand-alone benign threshold of ≥0.05%. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 and v4.1
FAF = 0.

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 The variant is absent from gnomAD (filtering allele frequency = 0), which is below the VCEP strong benign threshold of ≥0.025%. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 and v4.1
FAF = 0.

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 No data are available documenting this variant in healthy adult individuals. BS2 requires observation in a healthy adult for a dominant disorder with full penetrance expected at an early age. Details ▾Hide ▴

Evidence considered

No healthy adult carriers identified in available data.

BS4 No segregation data demonstrating lack of co-segregation with disease are available. BS4 requires at least one informative meiosis showing the variant does not segregate with the RASopathy phenotype. Details ▾Hide ▴

Evidence considered

No non-segregation data available.

BP2 No evidence of an alternative molecular cause for a RASopathy in HRAS (in cis/trans with another pathogenic variant) is available. BP2 requires point-based scoring from alternative molecular diagnoses. Details ▾Hide ▴

Evidence considered

No alternative molecular cause data available.

BP4 REVEL score of 0.811 exceeds the VCEP benign threshold of ≤0.3. Multiple lines of computational evidence support a deleterious effect (REVEL 0.811, BayesDel 0.249), contradicting BP4 application. Details ▾Hide ▴

Evidence considered

REVEL score: 0.811 (>0.3 threshold
fails BP4)
BayesDel score: 0.248544

Sources

revelbayesdel

BP5 No evidence of an alternative molecular basis for disease in a different gene is available. BP5 requires point-based scoring for an alternative molecular cause of a RASopathy. Details ▾Hide ▴

Evidence considered

No alternative molecular diagnosis data available.

Not assessed · 1 · no assessment recorded

PS3 Primary functional study publications for HRAS Q61R were not available for full-text review in the case folder. OncoKB curates HRAS Q61R as Likely Oncogenic/Likely Gain-of-function, and the structural biology literature (PMID:9219684) establishes that Gln61 is essential for GAP-mediated GTP hydrolysis — its mutation constitutively activates Ras. However, variant-specific functional data from VCEP-approved assays (RAS Activation, MEK Activation, ERK Activation) could not be verified from primary sources. Details ▾Hide ▴

Evidence considered

OncoKB: curated as Likely Gain-of-function
PMID:9219684: structural evidence that Gln61 mutation blocks GTPase activation

Still missing

Primary functional assay data for HRAS Q61R not available
VCEP-approved assay results needed to assign strength.

Sources

oncokb ↗PMID:9219684 ↗

Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 VCEPPVS1 is not applicable per the ClinGen RASopathy VCEP v2.3.0 for HRAS. This is a missense variant (p.Gln61Arg), not a null variant (nonsense, frameshift, or canonical splice variant). Details ▾Hide ▴

Evidence considered

Missense variant c.182A>G (p.Gln61Arg)
does not meet null-variant criteria per VCEP.

Sources

cspec ↗

PM3 VCEPPM3 is not applicable per the RASopathy VCEP; HRAS-related RASopathies are autosomal dominant disorders, not recessive. Details ▾Hide ▴

Evidence considered

VCEP marks PM3 as not applicable.

Sources

cspec ↗

PM4 N/APM4 applies to in-frame deletions/insertions and stop-loss variants causing protein length changes. This is a missense substitution. Details ▾Hide ▴

Evidence considered

Missense variant
PM4 is for in-frame indels and stop-loss.

PP2 VCEPPP2 is not applicable per the RASopathy VCEP because the missense z-score for HRAS is <3.09 in gnomAD. Details ▾Hide ▴

Evidence considered

VCEP rule: PP2 not applicable
HRAS missense z-score < 3.09.

Sources

cspec ↗

PP4 VCEPPP4 is not applicable per the RASopathy VCEP; phenotype specificity is assessed under PS4. Details ▾Hide ▴

Evidence considered

VCEP rule: PP4 not applicable
see PS4.

Sources

cspec ↗

PP5 VCEPPP5 is not for use per the ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation for this VCEP. Details ▾Hide ▴

Evidence considered

VCEP rule: PP5 explicitly marked 'Not Applicable for this VCEP'.

Sources

cspec ↗

BS3 VCEPBS3 is not applicable per the RASopathy VCEP for HRAS. Details ▾Hide ▴

Evidence considered

VCEP marks BS3 as not applicable.

Sources

cspec ↗

BP1 N/ABP1 per the RASopathy VCEP is specifically for truncating variants (nonsense, frameshift, canonical splice sites, initiation codon, gene deletions) in RASopathy genes where the disease mechanism is gain-of-function. This is a missense variant; BP1 does not apply. Details ▾Hide ▴

Evidence considered

VCEP BP1 rule: applies to truncating variants only in GOF genes
missense variant excluded.

Sources

cspec ↗

BP3 VCEPBP3 applies to in-frame deletions/insertions in repetitive regions; this is a missense substitution. Details ▾Hide ▴

No further detail was recorded.

BP6 VCEPBP6 is not for use per the ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation for this VCEP. Details ▾Hide ▴

Evidence considered

VCEP rule: BP6 explicitly marked 'Not Applicable for this VCEP'.

Sources

cspec ↗

BP7 N/ABP7 applies to synonymous variants with no predicted splice impact. This is a missense variant (p.Gln61Arg). Details ▾Hide ▴

Evidence considered

Missense variant
BP7 is specific to synonymous variants.

PS5 N/APS5 was not included in the adjudication list for this case. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene: HRAS
Transcript: NM_005343.4
Coding (HGVS c.): NM_005343.4:c.182A>G
Protein (HGVS p.): NP_005334.1:p.(Gln61Arg)
GRCh38: chr11:533874 T>C
GRCh37: chr11:533874 T>C
ClinVar: 160364
COSMIC: COSV54236691

Gene diagram

Every interpreted variant in HRAS, mapped onto the exon structure of NM_005343.4. Select a row to find it on the plot.

HRASNM_005343.4

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 HRAS — 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

Pangolin splice lossmagnitude shown

-0.010

Pangolin splice gain

0.010

Other predictors

REVEL: 0.811
BayesDel: 0.249

How the predictions were used

Evidence considered

REVEL score: 0.811 (≥0.7 threshold)
SpliceAI max delta: 0.00 (no splice impact)

Sources

revelspliceai ↗cspec ↗

Evidence considered

REVEL score: 0.811 (>0.3 threshold
fails BP4)
BayesDel score: 0.248544

Sources

revelbayesdel

BP7 N/ABP7 applies to synonymous variants with no predicted splice impact. This is a missense variant (p.Gln61Arg). Details ▾Hide ▴

Evidence considered

Missense variant
BP7 is specific to synonymous variants.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.811. BayesDel score = 0.248544.

10 paper records listed. 1 cited in the classification. None of the listed paper records explicitly indicates that the variant is named.

Cited in the classification

The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants.

Solved the crystal structure of the H-Ras-RasGAP complex at 2.5A resolution. Demonstrated that glutamine-61 of Ras is essential for GTP hydrolysis; its mutation to any amino acid except glutamate blocks GAP-mediated GTPase activation and locks Ras in the active GTP-bound state. The structural mechanism explains why codon 61 substitutions (including Q61R) are oncogenic, but the specific NM_005343.4:c.182A>G variant was not individually tested.
→ PM1 Does not name this variant
PMID 9219684 ↗
Source detail

Glutamine-61 is essential for GTP hydrolysis: Its mutation to any other amino acid (except Glu) blocks Ras-mediated GTP hydrolysis by GAP.

Location Abstract; Fig. 4C caption (Gln61 structural role); Results, switch II discussion

Context X-ray crystallography of H-Ras-GDP-AlF3-GAP-334 ternary complex

Other recorded publications

ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer.

Analyzed H-, K-, and N-ras mutations in 125 thyroid carcinoma specimens. HRAS was mutated in 5 of 107 tumors. HRAS codon 61 mutations identified were Q61L (CAG>CTG) and Q61P (CAG>GGG). NM_005343.4:c.182A>G (p.Gln61Arg) was not identified in this study.
Does not name this variant
PMID 12947056 ↗
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

Population-scale mutational hotspot analysis across 11,119 tumors from 41 cancer types. Identified codon Q61 as a statistically significant hotspot in HRAS and NRAS, predominantly in papillary thyroid cancers. Validated RAC1 Q61R (paralogous to HRAS Q61) as an activating mutation in vitro. HRAS Q61R was not specifically analyzed as an individual variant.
Does not name this variant
PMID 26619011 ↗
Quoted passage
cells expressing RAC1 Q61R, a mutation we identified in a primary prostate cancer that is paralogous to KRAS Q61, also potently induced RAC1 activation
Results, 'Lineage diversity and mutant allele-specificity'; Fig 3a; Fig 4d-f
Pattern of ras and gsp oncogene mutations in radiation-associated human thyroid tumors.

No paper-specific finding is recorded.

PMID 7630645 ↗
High mutation frequency in ras genes of skin tumors isolated from DNA repair deficient xeroderma pigmentosum patients.

No paper-specific finding is recorded.

PMID 8453633 ↗
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.

ACMG/AMP standards and guidelines for sequence variant interpretation. General framework document that does not discuss any specific variant.
Does not name this variant
PMID 25741868 ↗
Mutational dynamics between primary and relapse neuroblastomas.

Schramm A et al. · 2015

Whole-exome sequencing of 16 paired primary and relapse neuroblastomas. Identified HRAS p.Gly13Arg in one primary tumor retained at relapse. NM_005343.4:c.182A>G (p.Gln61Arg) was not reported.
Does not name this variant
PMID 26121086 ↗
Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations.

Eleveld TF et al. · 2015

Whole-genome sequencing of 23 paired diagnostic and relapse neuroblastomas. Identified RAS-MAPK pathway mutations including ALK, NRAS, KRAS, HRAS, BRAF, PTPN11, and NF1. Specific HRAS Q61R was not reported among the identified mutations.
Does not name this variant
PMID 26121087 ↗
American College of Medical Genetics and Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in neoplastic disorders.

No paper-specific finding is recorded.

PMID 23619274 ↗
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).

Authors/Task Force members et al. · 2014

No paper-specific finding is recorded.

PMID 25173338 ↗

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 3 Likely pathogenic · 1 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

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 Likely pathogenic (3 clinical laboratories) and as Pathogenic (1 clinical laboratory). (ClinVarID = 160364)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.811. BayesDel score = 0.248544.

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; COSV54236691, n = 417 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.