NRASc.38G>TUncertain significance

Print report

Variant interpretation report

NRAS c.38G>T, p.(Gly13Val)

NM_002524.5:c.38G>T NP_002515.1:p.(Gly13Val) View identifiers

Classification

Uncertain significance

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.

Uncertain.The recorded classification is uncertain significance.

In plain language

Gene-level background from the recorded interpretation.

About NRAS

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 moderate (pathogenic) · 2 supporting (pathogenic)
Expert rules: ClinGen NRAS VCEP v1.0
Other laboratories (ClinVar): 2 Likely pathogenic
Pipeline record: 20 Jul 2026 · version 7.0.4

Evidence considered

View criteria

Applied evidence criteria

PM1 (moderate): Gly13 in NRAS lies within the P-loop domain (residues 10-17 in HRAS, analogous in NRAS), which is an approved functional domain in the RASopathy VCEP supplemental material (Alignment with PM1 domains). This is also a statistically significant mutational hotspot per cancerhotspots.org. The VCEP specifies moderate strength for PM1 application at approved functional domains. The P-loop is critical for nucleotide binding and GTPase activity.
PP2 (supporting): The RASopathy VCEP states that PP2 is applicable to all RASopathy genes described and curated. NRAS is a RASopathy gene with a low rate of benign missense variation where missense variants are a common mechanism of disease. This is a missense variant (p.Gly13Val).
PP3 (supporting): Multiple lines of computational evidence support a deleterious effect. REVEL score of 0.789 predicts damaging. BayesDel score of 0.314 supports a deleterious effect. SpliceAI delta score of 0.00 indicates no splicing impact. The VCEP specifies supporting strength for PP3 when multiple lines of computational evidence support a deleterious effect.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.

01The reasoning

How it was classified

The recorded framework is ClinGen NRAS VCEP v1.0. 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: 3 Benign evidence criteria: 0

Pathogenic criteria applied · 3

PM1Moderate

PM1 · moderate

Gly13 in NRAS lies within the P-loop domain (residues 10-17 in HRAS, analogous in NRAS), which is an approved functional domain in the RASopathy VCEP supplemental material (Alignment with PM1 domains). This is also a statistically significant mutational hotspot per cancerhotspots.org. The VCEP specifies moderate strength for PM1 application at approved functional domains. The P-loop is critical for nucleotide binding and GTPase activity.

PP2Supporting

PP2 · supporting

The RASopathy VCEP states that PP2 is applicable to all RASopathy genes described and curated. NRAS is a RASopathy gene with a low rate of benign missense variation where missense variants are a common mechanism of disease. This is a missense variant (p.Gly13Val).

PP3Supporting

PP3 · supporting

Multiple lines of computational evidence support a deleterious effect. REVEL score of 0.789 predicts damaging. BayesDel score of 0.314 supports a deleterious effect. SpliceAI delta score of 0.00 indicates no splicing impact. The VCEP specifies supporting strength for PP3 when multiple lines of computational evidence support a deleterious effect.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Uncertain significance

ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1.0 v1.0 lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM1 moderate, PP2 supporting, PP3 supporting; combination = 1 moderate + 2 supporting, which maps to VUS.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1

gnomAD v2.1

Population frequency

1 / 1,614,026 alleles

gnomAD v4.1: 1 / 1,614,026 alleles. Recorded AF 6.19569e-07. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 3.97627e-06; MAF= 0.00040%, 1/251492 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.78997e-06; MAF= 0.00088%, 1/113766 alleles, homozygotes = 0).

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

No listed criterion applied

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

SpliceAI score

0.000 maximum delta

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

Applied · PP3 → SpliceAI ↗

ClinVar submissions

2 reported laboratory submissions

2 Likely 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

141 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV54736480, n = 141 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 NRAS VCEP v1.0, with the data and sources behind each one.

27 criteria with recorded statuses: 3 met · 7 not met · 9 not assessed · 8 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 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

c.38G>T (p.Gly13Val) is located in the P-loop domain (residues 10-17), an approved functional domain critical for GTP binding and hydrolysis in NRAS, satisfying PM1 at moderate strength per the ClinGen RASopathy VCEP.

PP2 is met at supporting strength as this is a missense variant in NRAS, a RASopathy gene where missense variants are a common mechanism of disease, per the VCEP specification.

Multiple in silico tools predict a deleterious effect (REVEL = 0.789, BayesDel = 0.314), satisfying PP3 at supporting strength per the VCEP.

The variant is present at extremely low frequency in gnomAD (v2.1: 1/251,492; v4.1: 1/1,614,026) and is absent from gnomAD-Canada, consistent with a rare disease-causing variant, though PM2 is not met per strict VCEP requirement for complete absence.

The variant has been reported in ClinVar as Likely pathogenic by two clinical laboratories (ClinVar ID 375876) and is annotated as Likely Oncogenic by OncoKB with 141 somatic occurrences in COSMIC, supporting its functional significance, though these alone do not independently meet PS4 or PS5 criteria per VCEP rules.

PVS1, PP5, BP6, PP4 are not applicable per the RASopathy VCEP specification. BP1 is not applicable as this is a missense variant, not a truncating variant. BP7 is not applicable as this is not a synonymous variant.

Met · 3

PM1 ModerateGly13 in NRAS lies within the P-loop domain (residues 10-17 in HRAS, analogous in NRAS), which is an approved functional domain in the RASopathy VCEP supplemental material (Alignment with PM1 domains). This is also a statistically significant mutational hotspot per cancerhotspots.org. The VCEP specifies moderate strength for PM1 application at approved functional domains. The P-loop is critical for nucleotide binding and GTPase activity. Details ▾Hide ▴

Evidence considered

P-loop domain (residues analogous to HRAS 10-17) is VCEP-approved PM1 domain
Gly13 lies within the P-loop
Statistically significant hotspot per cancerhotspots.org
COSMIC: 141 somatic occurrences at this residue/adjacent

Sources

cspec ↗vcep_alignment_with_pm1_domains_pptxoncokb ↗PMID:9219684 ↗

PP2 SupportingThe RASopathy VCEP states that PP2 is applicable to all RASopathy genes described and curated. NRAS is a RASopathy gene with a low rate of benign missense variation where missense variants are a common mechanism of disease. This is a missense variant (p.Gly13Val). Details ▾Hide ▴

Evidence considered

VCEP: PP2 is applicable to all RASopathy genes
NRAS is a RASopathy gene
Variant is missense

Sources

cspec ↗

PP3 SupportingMultiple lines of computational evidence support a deleterious effect. REVEL score of 0.789 predicts damaging. BayesDel score of 0.314 supports a deleterious effect. SpliceAI delta score of 0.00 indicates no splicing impact. The VCEP specifies supporting strength for PP3 when multiple lines of computational evidence support a deleterious effect. Details ▾Hide ▴

Evidence considered

REVEL score: 0.789 (damaging)
BayesDel score: 0.314 (supports deleterious)
SpliceAI max delta: 0.00 (no splice impact)

Sources

revelbayesdelspliceai ↗

Not met · 7 · evaluated, threshold not reached

PS1 PS1 requires the same amino acid change (p.Gly13Val) to have been previously established as pathogenic per VCEP criteria via a different nucleotide change. No evidence was found that another nucleotide change producing p.Gly13Val in NRAS (e.g., c.38G>A) has been classified as pathogenic in the germline RASopathy context. While the VCEP permits application across analogous residues in Group 1 genes (HRAS, NRAS, KRAS), and G13V in HRAS is a known Costello syndrome variant, insufficient VCEP-level evidence was present in the case materials to confirm this. Details ▾Hide ▴

Evidence considered

VCEP PS1 rule requires previously established pathogenic variant per VCEP criteria
No evidence of alternate nucleotide change producing p.Gly13Val classified as P in germline

Still missing

No VCEP-level classification data for HRAS G13V or KRAS G13 pathogenic variants

Sources

cspec ↗clinvar ↗

PS3 The RASopathy VCEP requires approved functional studies supporting a damaging effect at Strong strength. The VCEP-approved functional assays for NRAS (RAS activation: PMIDs 19966803, 28594414, 21263000; MEK activation: same PMIDs; ERK activation: 19966803, 28594414) are validated at PS3_Supporting level with control variants G12V, I24N, T58I, and G60E. The p.Gly13Val variant was not directly tested in any of the approved functional study publications. While Gly13 is adjacent to the validated Gly12 residue in the P-loop, the VCEP PS3 criterion only permits Strong strength and the variant falls outside the set of directly validated controls. Domain-level inference from adjacent residue testing does not meet PS3 criteria. Details ▾Hide ▴

Evidence considered

VCEP-approved NRAS assays validated with G12V
I24N
T58I
G60E but not G13V
PS3 only applicable at Strong per VCEP
G13V not directly tested in approved functional studies

Still missing

No direct functional testing of p.Gly13Val in VCEP-approved assays

Sources

cspec ↗vcep_svi_rasopathy_vcep_v2_approved_functional_studiesPMID:9219684 ↗PMID:20371679 ↗PMID:33637626 ↗

PM2 The RASopathy VCEP requires complete absence from all population databases. This variant is present in gnomAD v2.1 at 1/251,492 alleles (AF = 3.98 × 10⁻⁶) and in gnomAD v4.1 at 1/1,614,026 alleles (AF = 6.20 × 10⁻⁷). Although extremely rare, the variant is not completely absent, and the VCEP threshold for PM2 is not satisfied. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: 1/251
492 alleles (AF = 3.98e-06
NFE)
gnomAD v4.1: 1/1
614
026 alleles (AF = 6.20e-07

Sources

gnomad_v2 ↗gnomad_v4 ↗

BA1 The RASopathy VCEP sets the BA1 threshold at allele frequency ≥0.05%. This variant has an allele frequency of 3.98 × 10⁻⁶ (0.0004%) in gnomAD v2.1 and 6.20 × 10⁻⁷ (0.00006%) in gnomAD v4.1, well below the VCEP threshold. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF: 0.00040%
gnomAD v4.1 AF: 0.00006%
VCEP BA1 threshold: ≥0.05%

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 The RASopathy VCEP sets the BS1 threshold at allele frequency ≥0.025%. This variant has an allele frequency of 3.98 × 10⁻⁶ (0.0004%) in gnomAD v2.1 and 6.20 × 10⁻⁷ (0.00006%) in gnomAD v4.1, well below the VCEP threshold. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF: 0.00040%
gnomAD v4.1 AF: 0.00006%
VCEP BS1 threshold: ≥0.025%

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS3 BS3 requires approved functional studies showing no damaging effect on protein function. The VCEP-approved functional studies for NRAS are the same assays approved for PS3 (RAS, MEK, ERK activation). No functional data showing a benign effect for p.Gly13Val was identified. The variant was not directly tested in the approved functional studies, and no published data demonstrates a neutral functional effect. Details ▾Hide ▴

Evidence considered

VCEP-approved NRAS assays do not include G13V testing
No published benign functional data for G13V

Sources

cspec ↗vcep_svi_rasopathy_vcep_v2_approved_functional_studiesPMID:9219684 ↗

BP4 BP4 requires multiple lines of computational evidence suggesting no impact on gene or gene product. REVEL (0.789) and BayesDel (0.314) both predict a deleterious effect, contradicting BP4. In silico evidence supports pathogenicity (PP3) rather than benign impact. Details ▾Hide ▴

Evidence considered

REVEL score: 0.789 (damaging
does not support benign)
BayesDel score: 0.314 (does not support benign)
In silico evidence supports PP3
not BP4

Sources

revelbayesdelspliceai ↗

Not assessed · 9 · no assessment recorded

PS2 PS2 requires a confirmed de novo occurrence (paternity confirmed) in a patient with RASopathy and no family history. No de novo data for NM_002524.5:c.38G>T was identified in the case materials. Details ▾Hide ▴

Still missing

No de novo data available in case materials

PS4 PS4 requires counting independent proband occurrences. The variant is present in ClinVar as Likely pathogenic from 2 clinical laboratories and is reported in COSMIC with 141 somatic occurrences. However, specific germline proband count data with adjudicable phenotype was not available in the case materials. PMID 19775298 (De Filippi 2009) describes a germline NRAS mutation in a JMML patient, but full text was unavailable to confirm proband details. Details ▾Hide ▴

Evidence considered

ClinVar: LP by 2 clinical labs
COSMIC: 141 somatic occurrences
OncoKB: Likely Oncogenic annotation

Still missing

No verified germline proband count data
PMID 19775298 full text unavailable

Sources

clinvar ↗oncokb ↗

PM5 The RASopathy VCEP PM5 rule states it should not be used as an independent criterion in conjunction with PM1 when the residue is a designated mutational hot-spot. Since Gly13 is in the PM1-approved P-loop domain and PM1 is met at moderate, PM5 cannot be independently applied per VCEP rules to avoid premature designation of likely pathogenic classification in the absence of other evidence. Details ▾Hide ▴

Evidence considered

VCEP PM5 rule explicitly bars independent use with PM1 for hot-spot residues
PM1 is met for the P-loop domain containing Gly13

Sources

cspec ↗

PM6 PM6 requires a confirmed de novo observation without confirmation of paternity and maternity. No de novo data for NM_002524.5:c.38G>T was identified in the case materials. PMID 19775298 may describe a germline case, but full text was unavailable for verification. Details ▾Hide ▴

Still missing

No de novo data available

PP1 PP1 requires co-segregation data with at least three informative meioses per VCEP (supporting level). No segregation data was available in the case materials. Details ▾Hide ▴

Still missing

No segregation or family data available

BS2 The RASopathy VCEP states that general population data should not be used for BS2 due to variable expressivity and severity of RASopathies. Clinical laboratories are encouraged to accumulate more than 3 instances of well-phenotyped family members before applying this criterion. No such data was available in the case materials. Details ▾Hide ▴

Still missing

No well-phenotyped healthy adult carrier data available

Sources

cspec ↗

BS4 The RASopathy VCEP requires only one informative meiosis to apply BS4 at strong strength. No segregation data was available in the case materials. Details ▾Hide ▴

Still missing

No segregation data available

BP2 BP2 requires observation in trans with a pathogenic variant for a fully penetrant dominant disorder, or in cis with a pathogenic variant. No such data was available in the case materials. Details ▾Hide ▴

Still missing

No phase data available

BP5 BP5 requires the variant to be found in a case with an alternate molecular basis for disease. No such data was available in the case materials. Details ▾Hide ▴

Still missing

No data on alternate molecular basis

Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 VCEPThe ClinGen RASopathy VCEP explicitly designates PVS1 as not applicable for RASopathy genes including NRAS, because loss of function and/or haploinsufficiency have not been clearly identified as disease mechanisms for these genes relative to the RASopathy spectrum phenotype. This is a missense variant (p.Gly13Val), further precluding PVS1 application. Details ▾Hide ▴

Evidence considered

VCEP explicitly states PVS1 is Not Applicable for this VCEP for RASopathy genes
Variant is a missense substitution
not a null variant

Sources

cspec ↗

PP4 VCEPDesignated Not Applicable by the ClinGen RASopathy VCEP. The VCEP states this criterion is not applicable to the RASopathies; see PS4 criterion for proband counting options. Details ▾Hide ▴

Evidence considered

VCEP explicitly designates PP4 as Not Applicable

Sources

cspec ↗

PP5 VCEPDesignated Not Applicable by the ClinGen RASopathy VCEP. This criterion is not for use as recommended by the ClinGen SVI VCEP Review Committee. Details ▾Hide ▴

Evidence considered

VCEP explicitly designates PP5 as Not Applicable

Sources

cspec ↗

BP1 N/AThe RASopathy VCEP specifies BP1 for truncating variants (nonsense, frameshift, canonical splice sites, initiation codon, entire gene or multi-exon deletion) in genes without established LOF correlation to disease. This is a missense variant (p.Gly13Val), not a truncating variant. BP1 is not applicable. Details ▾Hide ▴

Evidence considered

VCEP BP1 rule is for truncating variants only
This is a missense variant

Sources

cspec ↗

BP3 N/AThis is a single-nucleotide substitution, not an in-frame deletion/insertion in a repetitive region. Details ▾Hide ▴

No further detail was recorded.

BP6 VCEPDesignated Not Applicable by the ClinGen RASopathy VCEP. This criterion is not for use as recommended by the ClinGen SVI VCEP Review Committee. Details ▾Hide ▴

Evidence considered

VCEP explicitly designates BP6 as Not Applicable

Sources

cspec ↗

BP7 N/ABP7 is for synonymous (silent) variants with no predicted splice impact. This is a missense variant (p.Gly13Val), not a synonymous variant. Details ▾Hide ▴

Evidence considered

Variant is missense
not synonymous

PS5 N/ADesignated Not Applicable by the ClinGen RASopathy VCEP. This criterion is not for use as recommended by the ClinGen SVI VCEP Review Committee. Details ▾Hide ▴

Evidence considered

VCEP explicitly designates PS5 (PP5) as Not Applicable

Sources

cspec ↗

Identifiers

Gene: NRAS
Transcript: NM_002524.5
Coding (HGVS c.): NM_002524.5:c.38G>T
Protein (HGVS p.): NP_002515.1:p.(Gly13Val)
GRCh38: chr1:114716123 C>A
GRCh37: chr1:115258744 C>A
ClinVar: 375876, 13899
COSMIC: COSV54736480

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

	Protein	Location	Classification	Link

gnomAD v4.1 1 / 1,614,026 alleles AF 6.2e-07 · 0 homozygotes

gnomAD v2.1 1 / 251,492 alleles AF 3.98e-06 · 0 homozygotes

gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 6.2e-07 · 1 / 1,614,026 alleles · 0 hom

European (non-Finnish)1 / 1,179,892

8.5e-07

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

gnomAD v2.1

AF 4e-06 · 1 / 251,492 alleles · 0 hom

European (non-Finnish)1 / 113,766

8.8e-06

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

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 6.19569e-07; MAF= 0.00006%, 1/1614026 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.47535e-07; MAF= 0.00008%, 1/1179892 alleles, homozygotes = 0).

gnomAD v2.1

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat +172 bp

0.000

SpliceAI acceptor gainat +54 bp

0.000

SpliceAI donor lossat +4 bp

0.000

SpliceAI donor gainat -73 bp

0.000

Pangolin splice lossmagnitude shown

-0.000

Pangolin splice gain

0.000

Other predictors

REVEL: 0.789
BayesDel: 0.314

How the predictions were used

Evidence considered

REVEL score: 0.789 (damaging)
BayesDel score: 0.314 (supports deleterious)
SpliceAI max delta: 0.00 (no splice impact)

Sources

revelbayesdelspliceai ↗

Evidence considered

REVEL score: 0.789 (damaging
does not support benign)
BayesDel score: 0.314 (does not support benign)
In silico evidence supports PP3
not BP4

Sources

revelbayesdelspliceai ↗

BP7 N/ABP7 is for synonymous (silent) variants with no predicted splice impact. This is a missense variant (p.Gly13Val), not a synonymous variant. Details ▾Hide ▴

Evidence considered

Variant is missense
not synonymous

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.789. BayesDel score = 0.314125.

8 paper records listed. 1 cited in the classification.

Cited in the classification

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

Crystal structure of the Ras-RasGAP complex at 2.5 Å resolution. Glycine-12 is identified as within van der Waals distance of both Arg789 of GAP-334 and Gln61 of Ras; even its mutation to alanine would disrupt transition-state arrangements. Glycine-13 is noted as more remote from GAP-334. The P-loop (residues 10-16) is characterized as critical for phosphate binding and GTPase activity.
→ PM1 Does not name this variant
PMID 9219684 ↗
Source detail

Glycine-13 is more remote from GAP-334.

Location Results; Figure 4C and caption

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

Other recorded publications

RAS mutations contribute to evolution of chronic myelomonocytic leukemia to the proliferative variant.

Ricci C et al. · 2010

NRAS G13V (GGT→GTT) mutation identified as a somatic event in chronic myelomonocytic leukemia (CMML) patients during disease progression from myelodysplastic to myeloproliferative phase. Allele-specific PCR documented clonal expansion of the G13V-harboring clone in two patients, supporting its role as a secondary mutation contributing to proliferative advantage.
Names this variant
PMID 20371679 ↗
Quoted passage
allele-specific PCR allowed to follow the consecutive occurrence of two clones harboring the NRAS G13V (GGT→GTT) and G12R
Results, Table 2 and Discussion; Figure 5D
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

Pan-cancer analysis of 11,119 tumors identifying 470 statistically significant mutational hotspots across 275 genes. NRAS codon 12 and 13 mutations are noted as prevalent in AML, colorectal, bladder, and head and neck cancers, distinct from the NRAS Q61 mutations predominant in thyroid cancer. The specific G13V variant is not individually discussed.
Does not name this variant
PMID 26619011 ↗
Quoted passage
there was a higher prevalence of G12 and 13 codon mutations in these genes in AMLs, colorectal, bladder, and head and neck cancers
Results, 'Lineage diversity and mutant allele-specificity' section
AACR Project GENIE: Powering Precision Medicine through an International Consortium.

Description of the AACR Project GENIE consortium for sharing cancer genomic and clinical outcome data. No specific variant is discussed.
Does not name this variant
PMID 28572459 ↗
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. Patients with codon 12/13 NRAS mutations had significantly shorter PFS and OS compared to codon 61 mutations when treated with the MEK inhibitor. The specific G13V variant is not individually reported, though codon 13 mutations (including G13C) are discussed.
Does not name this variant
PMID 33637626 ↗
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
Results, Tables 1-2, Discussion
Mutational analysis of PDGFR-RAS/MAPK pathway activation in childhood medulloblastoma.

Gilbertson RJ et al. · 2006

Mutational analysis of PDGFR-RAS/MAPK pathway in 28 childhood medulloblastomas. No oncogenic mutations were identified in NRAS, KRAS, HRAS, BRAF, or PDGFRB in any case. The study demonstrates that activating mutations in established mutational hotspots within the PDGFR-RAS/MAPK pathway are rare in medulloblastoma.
Does not name this variant
PMID 16434186 ↗
Quoted passage
No sequence variations were identified for any of these genes in any of the tumour samples.
Results and Discussion
Comprehensive genomic analysis of rhabdomyosarcoma reveals a landscape of alterations affecting a common genetic axis in fusion-positive and fusion-negative tumors.

Shern JF et al. · 2014

Comprehensive genomic analysis of 147 rhabdomyosarcoma tumors. NRAS mutations at codons 12, 13, or 61 were found in 11.7% of fusion-negative tumors, predominantly in the embryonal subtype. The specific NM_002524.5:c.38G>T (p.Gly13Val) variant was not individually reported.
Does not name this variant
PMID 24436047 ↗
Quoted passage
Alterations in RAS genes, NRAS (PFN frequency, 11.7%), KRAS (PFN 6.4%), HRAS (PFN 4.3%) affected the oncogenic codons 12, 13 or 61
Results, 'RAS/PIK3CA/Tyrosine Kinase Mutations' section
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 the interpretation of sequence variants. Provides the generic framework for variant classification but does not discuss any specific variant.
Does not name this variant
PMID 25741868 ↗

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

gnomAD v4.1 1 / 1,614,026 recorded alleles Open source ↗

gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗

SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗

ClinVar 2 Likely 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

gnomAD v2.1

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Likely pathogenic (2 clinical laboratories). (ClinVarID = 375876)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.789. BayesDel score = 0.314125.

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; COSV54736480, n = 141 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.