GNA11c.626A>TPathogenic

Print report

Variant interpretation report

GNA11 c.626A>T, p.(Gln209Leu)

NM_002067.5:c.626A>T NP_002058.2:p.(Gln209Leu) 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 GNA11

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 strong (pathogenic) · 1 moderate (pathogenic) · 4 supporting (pathogenic)
Expert rules: Not recorded
Other laboratories (ClinVar): 1 Pathogenic · 1 Likely pathogenic
Pipeline record: 18 Jun 2026

Evidence considered

View criteria

Applied evidence criteria

PS3 (strong): Well-established in vitro and in vivo functional studies demonstrate that GNA11 Q209L is a gain-of-function activating mutation. Van Raamsdonk et al. (2010) showed Q209L-transduced melan-a cells produced rapidly growing tumors in 6/6 injection sites in immunocompromised mice versus 0/14 controls. Moore et al. (2018) generated a conditional GNA11 Q209L mouse model that recapitulated human Gq-associated melanomas with pigmented neoplastic lesions in skin, eye, and leptomeninges. These independent lines of functional evidence confirm a deleterious gain-of-function effect.
PS4 (moderate): This variant is highly enriched in affected individuals compared to the general population. It is absent from gnomAD v2.1, v4.1, and gnomAD-Canada across all populations, yet is recurrently observed in affected tissue: COSMIC reports 442 somatic occurrences predominantly in uveal melanoma and blue nevi; it has been reported in multiple publications as the predominant GNA11 codon 209 mutation in melanocytic neoplasms; and is classified as Pathogenic/Likely Pathogenic in ClinVar. The extreme disparity between population absence and disease-associated presence supports a pathogenic role, though evidence derives predominantly from somatic and mosaic contexts.
PM2 (supporting): This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada v1.0, indicating it is extremely rare or absent in the general population, consistent with a pathogenic role.
PP2 (supporting): GNA11 has a low rate of benign missense variation in population databases, and missense variants are the predominant pathogenic mechanism (gain-of-function at hotspot codons 183 and 209). The gene is constrained for missense variation, supporting PP2.
PP3 (supporting): In silico prediction supports a deleterious effect: REVEL score is 0.833 (strongly damaging). SpliceAI predicts no splicing impact (max delta score 0.01). BayesDel score is 0.246, borderline below typical damaging threshold. The REVEL score, combined with the location in a critical functional domain, supports a deleterious computational prediction.
PP5 (supporting): Two clinical laboratories have submitted this variant to ClinVar (variation ID 376002) with classifications of Pathogenic (SCV002525654, Seattle Children's Hospital) and Likely Pathogenic (SCV003804872, University Hospital Muenster). Both submissions are criteria-provided, single-submitter classifications. While no expert panel review is available, multiple independent clinical laboratories have reached concordant pathogenic conclusions.

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 Not recorded. 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: 6 Benign evidence criteria: 0

Pathogenic criteria applied · 6

PS3Strong

PS3 · strong

Well-established in vitro and in vivo functional studies demonstrate that GNA11 Q209L is a gain-of-function activating mutation. Van Raamsdonk et al. (2010) showed Q209L-transduced melan-a cells produced rapidly growing tumors in 6/6 injection sites in immunocompromised mice versus 0/14 controls. Moore et al. (2018) generated a conditional GNA11 Q209L mouse model that recapitulated human Gq-associated melanomas with pigmented neoplastic lesions in skin, eye, and leptomeninges. These independent lines of functional evidence confirm a deleterious gain-of-function effect.

PS4Moderate

PS4 · moderate

This variant is highly enriched in affected individuals compared to the general population. It is absent from gnomAD v2.1, v4.1, and gnomAD-Canada across all populations, yet is recurrently observed in affected tissue: COSMIC reports 442 somatic occurrences predominantly in uveal melanoma and blue nevi; it has been reported in multiple publications as the predominant GNA11 codon 209 mutation in melanocytic neoplasms; and is classified as Pathogenic/Likely Pathogenic in ClinVar. The extreme disparity between population absence and disease-associated presence supports a pathogenic role, though evidence derives predominantly from somatic and mosaic contexts.

PM2Supporting

PM2 · supporting

This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada v1.0, indicating it is extremely rare or absent in the general population, consistent with a pathogenic role.

PP2Supporting

PP2 · supporting

GNA11 has a low rate of benign missense variation in population databases, and missense variants are the predominant pathogenic mechanism (gain-of-function at hotspot codons 183 and 209). The gene is constrained for missense variation, supporting PP2.

PP3Supporting

PP3 · supporting

In silico prediction supports a deleterious effect: REVEL score is 0.833 (strongly damaging). SpliceAI predicts no splicing impact (max delta score 0.01). BayesDel score is 0.246, borderline below typical damaging threshold. The REVEL score, combined with the location in a critical functional domain, supports a deleterious computational prediction.

PP5Supporting

PP5 · supporting

Two clinical laboratories have submitted this variant to ClinVar (variation ID 376002) with classifications of Pathogenic (SCV002525654, Seattle Children's Hospital) and Likely Pathogenic (SCV003804872, University Hospital Muenster). Both submissions are criteria-provided, single-submitter classifications. While no expert panel review is available, multiple independent clinical laboratories have reached concordant pathogenic conclusions.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Pathogenic

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PS3 strong, PS4 moderate, PM2 supporting, PP2 supporting, PP3 supporting, PP5 supporting; combination = 1 strong + 1 moderate + 4 supporting, which 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

0.010 maximum delta

Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · PP3 → SpliceAI ↗

ClinVar submissions

2 reported laboratory submissions

1 Pathogenic · 1 Likely pathogenic.

Applied · PP5 → 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.

Applied · PS3 → OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

442 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV50017277, n = 442 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

26 criteria with recorded statuses: 6 met · 12 not met · 3 not assessed · 5 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 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

GNA11 c.626A>T (p.Gln209Leu) is a well-characterized gain-of-function missense variant at codon 209 within the switch II functional domain, a critical region for GTPase activity and a mutational hotspot in GNA11/GNAQ-driven melanocytic neoplasms.

Functional studies demonstrate a deleterious effect: Q209L-transduced melan-a cells produced rapidly growing tumors in all 6 injection sites in immunocompromised mice compared to 0 of 14 controls (PMID:21083380), and a conditional GNA11 Q209L knock-in mouse model recapitulated human Gq-associated melanomas with multi-organ neoplastic lesions (PMID:29490280).

The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada across all populations, yet is recurrently observed in affected tissue: COSMIC reports 442 somatic occurrences, and it has been identified as the predominant codon 209 mutation in uveal melanoma, blue nevi, cutaneous melanoma, and phakomatosis pigmentovascularis.

Two clinical laboratories in ClinVar classify this variant as Pathogenic or Likely Pathogenic (variation ID 376002). In silico prediction with REVEL (score 0.833) supports a damaging effect. GNA11 exhibits low benign missense variation in population databases, consistent with PP2.

Applying generic ACMG/AMP 2015 combination rules: PS3 (strong), PM1 (moderate), PS4 (moderate), PM2 (supporting), PP2 (supporting), PP3 (supporting), PP5 (supporting) support a classification of Pathogenic.

Met · 6

PS3 StrongWell-established in vitro and in vivo functional studies demonstrate that GNA11 Q209L is a gain-of-function activating mutation. Van Raamsdonk et al. (2010) showed Q209L-transduced melan-a cells produced rapidly growing tumors in 6/6 injection sites in immunocompromised mice versus 0/14 controls. Moore et al. (2018) generated a conditional GNA11 Q209L mouse model that recapitulated human Gq-associated melanomas with pigmented neoplastic lesions in skin, eye, and leptomeninges. These independent lines of functional evidence confirm a deleterious gain-of-function effect. Details ▾Hide ▴

Evidence considered

PMID:21083380: Q209L melan-a cell xenografts produced tumors in 6/6 sites vs 0/14 controls
PMID:29490280: conditional GNA11 Q209L mouse model recapitulated human uveal melanoma with multi-organ neoplastic lesions
OncoKB: Oncogenic classification
Gain-of-function

Sources

oncokb ↗

PS4 ModerateThis variant is highly enriched in affected individuals compared to the general population. It is absent from gnomAD v2.1, v4.1, and gnomAD-Canada across all populations, yet is recurrently observed in affected tissue: COSMIC reports 442 somatic occurrences predominantly in uveal melanoma and blue nevi; it has been reported in multiple publications as the predominant GNA11 codon 209 mutation in melanocytic neoplasms; and is classified as Pathogenic/Likely Pathogenic in ClinVar. The extreme disparity between population absence and disease-associated presence supports a pathogenic role, though evidence derives predominantly from somatic and mosaic contexts. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1
v4.1
and gnomAD-Canada
COSMIC: 442 somatic occurrences (COSV50017277)
PMID:21083380: Q209L found in 97.3% of GNA11 codon 209-mutated melanocytic neoplasms
PMID:26825879: Q209L reported in cutaneous melanoma
PMID:26778290: Q209L reported in phakomatosis pigmentovascularis
ClinVar: Pathogenic (1 submitter)
Likely pathogenic (1 submitter)

Still missing

Evidence derives predominantly from somatic/mosaic context
confirmed germline constitutional cases are limited
No formal case-control study with odds ratio calculation

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗clinvar ↗

PM2 SupportingThis variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada v1.0, indicating it is extremely rare or absent in the general population, consistent with a pathogenic role. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 (exomes)
Absent from gnomAD v4.1 (exomes)
Absent from gnomAD-Canada v1.0 (genomes)

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PP2 SupportingGNA11 has a low rate of benign missense variation in population databases, and missense variants are the predominant pathogenic mechanism (gain-of-function at hotspot codons 183 and 209). The gene is constrained for missense variation, supporting PP2. Details ▾Hide ▴

Evidence considered

GNA11 exhibits low benign missense variation in population databases
Missense gain-of-function variants at codons 183 and 209 are the established disease mechanism
GNA11 is constrained for missense variation (observed vs expected missense burden consistent with constraint)

Sources

gnomad_v2 ↗gnomad_v4 ↗

PP3 SupportingIn silico prediction supports a deleterious effect: REVEL score is 0.833 (strongly damaging). SpliceAI predicts no splicing impact (max delta score 0.01). BayesDel score is 0.246, borderline below typical damaging threshold. The REVEL score, combined with the location in a critical functional domain, supports a deleterious computational prediction. Details ▾Hide ▴

Evidence considered

REVEL: 0.833 (damaging)
BayesDel: 0.246 (borderline
below 0.27 threshold)
SpliceAI: max delta 0.01 (no splicing impact)

Still missing

BayesDel score (0.246) is borderline and does not independently support pathogenicity

Sources

revelbayesdelspliceai ↗

PP5 SupportingTwo clinical laboratories have submitted this variant to ClinVar (variation ID 376002) with classifications of Pathogenic (SCV002525654, Seattle Children's Hospital) and Likely Pathogenic (SCV003804872, University Hospital Muenster). Both submissions are criteria-provided, single-submitter classifications. While no expert panel review is available, multiple independent clinical laboratories have reached concordant pathogenic conclusions. Details ▾Hide ▴

Evidence considered

ClinVar variation ID 376002: Pathogenic (1 submitter)
Likely pathogenic (1 submitter)
Both submissions are criteria-provided
single submitter

Still missing

No expert panel review or consensus classification available

Sources

clinvar ↗

Not met · 12 · evaluated, threshold not reached

PS2 No confirmed de novo occurrence with both parents tested negative. A mosaic case was reported in phakomatosis pigmentovascularis (PMID:26778290) but parental DNA was not tested and the event was postzygotic mosaic, not germline. Details ▾Hide ▴

Evidence considered

PMID:26778290 reported Q209L in mosaic state in a PPV patient
parents not tested

Still missing

No germline de novo event with confirmed paternity/maternity
Variant typically occurs as postzygotic mosaic
germline constitutional occurrence may be lethal

PM6 The variant was reported in a mosaic state in a patient with phakomatosis pigmentovascularis (PMID:26778290), but parents were not tested and the event was postzygotic mosaic rather than germline de novo. PM6 requires a confirmed de novo occurrence with both parents tested negative, which is not met. Details ▾Hide ▴

Evidence considered

PMID:26778290: Q209L detected in affected skin tissue in mosaic state
parental DNA not tested

Still missing

No germline de novo event with confirmed parental testing
Mosaicism precludes confident de novo assignment

PP1 No cosegregation data are available. All reported cases with this variant are sporadic, typically due to postzygotic mosaicism. Familial transmission has not been described, likely because the variant is lethal when constitutional and non-mosaic. Details ▾Hide ▴

Still missing

No multigenerational families available for cosegregation analysis
Variant predominantly occurs as postzygotic mosaic event

BA1 The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. Does not meet the BA1 allele frequency threshold of >1%. Details ▾Hide ▴

Evidence considered

Absent from all population databases

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

BS1 The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. Does not meet the BS1 allele frequency threshold of >0.3%. Details ▾Hide ▴

Evidence considered

Absent from all population databases

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

BS2 The variant is absent from all population databases. No evidence of observation in healthy homozygous adults or at allele frequencies consistent with recessive inheritance. Details ▾Hide ▴

Evidence considered

Absent from all population databases
no healthy homozygous carriers identified

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

BS3 Well-established in vitro and in vivo functional studies demonstrate that Q209L is a gain-of-function activating mutation, not a benign variant. Van Raamsdonk et al. (2010) showed Q209L produced tumors in 6/6 xenograft sites. Moore et al. (2018) demonstrated GNA11 Q209L mice recapitulate human melanoma. No functional evidence supports a benign effect. Details ▾Hide ▴

Evidence considered

PMID:21083380: Q209L is oncogenic in xenograft assays (6/6 tumors)
PMID:29490280: GNA11 Q209L mouse model develops melanocytic neoplasms

BP1 GNA11-related disorders are caused by gain-of-function missense variants at hotspot codons (primarily 209 and 183), not by truncating variants. BP1, which applies when truncating variants are the primary disease mechanism, is not applicable to GNA11. Details ▾Hide ▴

Evidence considered

GNA11 disease mechanism is gain-of-function via missense mutations at hotspot codons
not loss-of-function via truncating variants

BP4 REVEL predicts a damaging effect (score 0.833), contradicting a benign computational assessment. SpliceAI predicts no splicing impact (max delta 0.01), but this single benign line is insufficient to meet BP4, which requires multiple lines of computational evidence suggesting no impact. Details ▾Hide ▴

Evidence considered

REVEL: 0.833 (damaging
contradicts BP4)
SpliceAI: max delta 0.01 (no splicing impact
but insufficient alone for BP4)

Still missing

Only SpliceAI supports a benign prediction
REVEL contradicts it. Multiple benign lines are required for BP4.

Sources

revelspliceai ↗

BP5 No evidence has been identified that affected individuals carrying this variant have an alternate molecular basis for their phenotype. BP5 requires demonstration of a definitive alternate genetic cause in a case harboring this variant. Details ▾Hide ▴

Still missing

No cases identified where an alternate molecular cause was found in individuals carrying this variant

BP6 ClinVar reports this variant as Pathogenic and Likely Pathogenic (variation ID 376002). No reputable source classifies this variant as benign or likely benign. BP6 requires a reputable source to report the variant as benign. Details ▾Hide ▴

Evidence considered

ClinVar: Pathogenic (1 submitter)
Likely pathogenic (1 submitter) — not benign

Sources

clinvar ↗

PS5 No different missense change at the same residue (Gln209) has been independently established as pathogenic in a germline context. While Q209P, Q209L (by alternative nucleotide), and other codon 209 changes are observed somatically, they lack independent germline pathogenicity classification meeting PS5 requirements. Details ▾Hide ▴

Evidence considered

PMID:21083380 reports additional codon 209 changes (CAG→CCG/Q209P
CAG→CTA/Q209L-alt
CAG→CTT/Q209L-alt) but these lack independent germline pathogenicity classification

Still missing

No alternative nucleotide change at codon 209 with established germline pathogenic classification

Not assessed · 3 · no assessment recorded

PS1 No alternative nucleotide change at codon 209 producing the same amino acid substitution (p.Gln209Leu) with an established independent pathogenic classification was identified. Details ▾Hide ▴

Still missing

No alternative nucleotide change producing p.Gln209Leu with established germline pathogenicity was found in ClinVar or literature.

PM1 The variant is located at codon 209 within the switch II domain of Gα11, a critical functional domain essential for GTP hydrolysis. Codon 209 is a well-established mutational hotspot in GNA11 and GNAQ, with multiple independent pathogenic missense substitutions reported at this residue (Q209L, Q209P, Q209H). Mutations at this hotspot result in constitutive activation of downstream MAPK signaling. Details ▾Hide ▴

Evidence considered

Codon 209 lies in the switch II functional domain of Gα11
critical for GTPase activity
PMID:21083380: multiple independent substitutions at codon 209 identified in melanocytic neoplasms
Statistically significant hotspot per cancerhotspots.org
GNA11/GNAQ codon 209 is one of the most recurrently mutated residues in uveal melanoma

PP4 Insufficient patient phenotype information is available for evaluation. ClinVar submissions list conditions as 'not provided' and 'see cases' without detailed clinical descriptions. The phenotypes associated with this variant (uveal melanoma, phakomatosis pigmentovascularis, cutaneous melanoma, blue nevi) are consistent with GNA11-related disorders, but specific patient-level phenotype data are not available for formal PP4 assessment. Details ▾Hide ▴

Evidence considered

ClinVar submissions lack detailed clinical phenotype descriptions ('not provided'
'see cases')

Still missing

No detailed patient phenotype data available in ClinVar submissions
Phenotype specificity to GNA11-related disorders cannot be formally assessed without individual-level data

Sources

clinvar ↗

Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/AThis variant is a missense change (c.626A>T, p.Gln209Leu), not a null variant (nonsense, frameshift, or canonical ±1,2 splice site). Generic PVS1 framework does not apply. Details ▾Hide ▴

No further detail was recorded.

PM5 N/ANo different pathogenic missense change at the same residue (Gln209) with a confirmed germline pathogenic classification was identified for PM5 comparator analysis. PM5 candidate harvesting was unable to confirm classic same-residue PM5 semantics. Details ▾Hide ▴

No further detail was recorded.

BS4 N/ABS4 requires demonstration of non-segregation in affected family members. This variant occurs predominantly in somatic/mosaic contexts with no multigenerational families available for segregation analysis. BS4 cannot be meaningfully assessed. Details ▾Hide ▴

No further detail was recorded.

BP2 N/AGNA11-related conditions are dominant (typically mosaic-dominant). This variant has never been reported in biallelic form. BP2, which applies to recessive disorders, is not applicable. Details ▾Hide ▴

No further detail was recorded.

BP7 N/AThis variant is a missense change (c.626A>T, p.Gln209Leu), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene: GNA11
Transcript: NM_002067.5
Coding (HGVS c.): NM_002067.5:c.626A>T
Protein (HGVS p.): NP_002058.2:p.(Gln209Leu)
GRCh38: chr19:3118944 A>T
GRCh37: chr19:3118942 A>T
ClinVar: 376002, 3238640
COSMIC: COSV50017277

Gene diagram

Every interpreted variant in GNA11, mapped onto the exon structure of NM_002067.5. Select a row to find it on the plot.

GNA11NM_002067.5

Fetching transcript structure from UCSC…

Exons

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Transcript span

—

Strand

—

Variants mapped

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Source

UCSC ncbiRefSeqCurated

All variants in GNA11 — 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

SpliceAI acceptor lossat +2 bp

0.000

SpliceAI acceptor gainat +73 bp

0.010

SpliceAI donor lossat -352 bp

0.000

SpliceAI donor gainat -116 bp

0.000

Pangolin splice lossmagnitude shown

-0.000

Pangolin splice gain

0.000

Other predictors

REVEL: 0.833
BayesDel: 0.246

How the predictions were used

Evidence considered

REVEL: 0.833 (damaging)
BayesDel: 0.246 (borderline
below 0.27 threshold)
SpliceAI: max delta 0.01 (no splicing impact)

Still missing

BayesDel score (0.246) is borderline and does not independently support pathogenicity

Sources

revelbayesdelspliceai ↗

Evidence considered

REVEL: 0.833 (damaging
contradicts BP4)
SpliceAI: max delta 0.01 (no splicing impact
but insufficient alone for BP4)

Still missing

Only SpliceAI supports a benign prediction
REVEL contradicts it. Multiple benign lines are required for BP4.

Sources

revelspliceai ↗

BP7 N/AThis variant is a missense change (c.626A>T, p.Gln209Leu), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴

No further detail was recorded.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.833. BayesDel score = 0.245583.

8 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.

Recorded publications

Mutations in GNA11 in uveal melanoma.

Van Raamsdonk CD et al. · 2010

No paper-specific finding is recorded.

PMID 21083380 ↗
GNA11 Mutation in a Patient With Cutaneous Origin Melanoma: A Case Report.

No paper-specific finding is recorded.

PMID 26825879 ↗
GNA11 Q209L Mouse Model Reveals RasGRP3 as an Essential Signaling Node in Uveal Melanoma.

No paper-specific finding is recorded.

PMID 29490280 ↗
The emerging mutational landscape of G proteins and G-protein-coupled receptors in cancer.

O'Hayre M et al. · 2013

No paper-specific finding is recorded.

PMID 23640210 ↗
Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations.

Chen X et al. · 2014

No paper-specific finding is recorded.

PMID 24141786 ↗
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.

Richards S et al. · 2015

No paper-specific finding is recorded.

PMID 25741868 ↗
Mosaic Activating Mutations in GNA11 and GNAQ Are Associated with Phakomatosis Pigmentovascularis and Extensive Dermal Melanocytosis.

Thomas AC et al. · 2016

No paper-specific finding is recorded.

PMID 26778290 ↗
American College of Medical Genetics and Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in neoplastic disorders.

Cooley LD et al. · 2013

No paper-specific finding is recorded.

PMID 23619274 ↗

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 0.010 Open source ↗

ClinVar 1 Pathogenic · 1 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 ↗

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 Pathogenic (1 clinical laboratory) and as Likely pathogenic (1 clinical laboratory). (ClinVarID = 376002)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.833. BayesDel score = 0.245583.

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; COSV50017277, n = 442 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.