About STK11
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
STK11 c.717G>C, p.(Trp239Cys)
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 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: 8
Benign evidence criteria: 0
Pathogenic criteria applied · 8
PS3Moderate
PS3 · moderate
Functional characterization by Boudeau et al. (2004, PMID:15561763) demonstrated that LKB1 mutants within the residue 239-242 cluster fail to bind STRADα-MO25α and lose catalytic activity. The study systematically tested 30 LKB1 catalytic domain point mutants in a co-expression/kinase assay in HEK293 cells and identified residues 239-242 as critical for LKB1 complex assembly and activation. While the exact p.Trp239Cys substitution was not individually tested, residue 239 falls within a systematically characterized critical functional cluster.
PS4Supporting
PS4 · supporting
The variant NM_000455.4:c.717G>C (p.Trp239Cys) was identified in a 42-year-old proband with Peutz-Jeghers syndrome (Scott et al., 2002, PMID:12372054). This single observation provides supporting-level evidence for pathogenicity.
PM1Moderate
PM1 · moderate
The p.Trp239Cys substitution is located within the STK11 kinase domain (codons 50-337) and specifically within the critical STRADα-MO25α binding region (residues 239-242). Functional studies by Boudeau et al. (2004, PMID:15561763) demonstrated that mutations in this cluster abolish LKB1 complex assembly and catalytic activity. Additionally, residue 239 is identified as a statistically significant hotspot in cancerhotspots.org.
PM2Supporting
PM2 · supporting
This variant is absent from gnomAD v2.1 (exomes), gnomAD v4.1 (exomes/genomes), and gnomAD-Canada v1.0, meeting the PM2 threshold for rare variant absent from population databases (allele frequency < 0.1%).
PP2Supporting
PP2 · supporting
STK11 is a well-established tumor suppressor gene in which missense variants are a recognized mechanism of disease. The gene has a low rate of benign missense variation and a high ratio of pathogenic to benign missense variants, supporting PP2 application for novel missense variants.
PP3Supporting
PP3 · supporting
REVEL predicts a damaging effect with a score of 0.859. SpliceAI predicts no significant splice impact (max delta score 0.15). BayesDel score is 0.484. Multiple lines of in silico evidence support a deleterious effect.
PP4Supporting
PP4 · supporting
The variant was identified in a patient with clinically confirmed Peutz-Jeghers syndrome (hamartomatous polyposis, mucocutaneous pigmentation), a phenotype highly specific for STK11. The proband in PMID:12372054 presented with hamartomatous intestinal polyps at age 42, consistent with PJS.
PP5Supporting
PP5 · supporting
This variant has been reported as Pathogenic in ClinVar (variation ID 7458) by a clinical testing laboratory (Labcorp/Invitae), with criteria provided. Although a single submitter without expert panel review limits weight, the clinical classification provides supporting evidence.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Likely 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 moderate, PS4 supporting, PM1 moderate, PM2 supporting, PP2 supporting, PP3 supporting, PP4 supporting, PP5 supporting; combination = 2 moderate + 6 supporting, which 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
0.150 maximum delta
Recorded SpliceAI maximum delta score: 0.150. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
1 reported laboratory submissions
1 Pathogenic. ClinVar API review status: criteria provided, single submitter.
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant lies in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
29 criteria with recorded statuses: 8 met · 12 not met · 4 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000455.4:c.717G>C (p.Trp239Cys) is a missense variant in STK11 exon 5, within the kinase domain and the critical STRADα-MO25α binding region (residues 239-242).
Functional characterization by Boudeau et al. (2004) demonstrated that LKB1 mutations within the 239-242 cluster abolish STRADα-MO25α binding and catalytic activity in a HEK293 co-expression assay, supporting a loss-of-function mechanism (PS3_moderate).
The variant is located in a well-established critical functional domain (kinase domain, STRADα-binding cluster) and at a statistically significant cancer hotspot, satisfying PM1 at moderate strength.
This variant was identified in a Peutz-Jeghers syndrome proband by Scott et al. (2002), presenting with hamartomatous polyposis diagnosed at age 42, a phenotype highly specific for STK11 (PS4_supporting, PP4_supporting).
The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases, meeting PM2 at supporting strength.
STK11 is a tumor suppressor gene with a low rate of benign missense variation, supporting PP2. Multiple in silico predictors (REVEL 0.859) indicate a deleterious effect (PP3). ClinVar reports the variant as Pathogenic with criteria provided by a clinical testing laboratory (PP5).
Applying generic ACMG/AMP 2015 combination rules: PS3_moderate + PM1_moderate + PM2_supporting + PP2_supporting + PP3_supporting + PP4_supporting + PP5_supporting + PS4_supporting. This meets the threshold for Pathogenic classification (2 moderate + ≥4 supporting criteria).
No criteria match.
Met · 8
PS3 ModerateFunctional characterization by Boudeau et al. (2004, PMID:15561763) demonstrated that LKB1 mutants within the residue 239-242 cluster fail to bind STRADα-MO25α and lose catalytic activity. The study systematically tested 30 LKB1 catalytic domain point mutants in a co-expression/kinase assay in HEK293 cells and identified residues 239-242 as critical for LKB1 complex assembly and activation. While the exact p.Trp239Cys substitution was not individually tested, residue 239 falls within a systematically characterized critical functional cluster. Details ▾Hide ▴
Evidence considered
- Boudeau et al. 2004: 30 LKB1 mutants tested in HEK293 co-expression with STRADα-MO25α
- mutations at residues 239-242 abolished STRADα binding and catalytic activity toward LKBtide substrate. Single study with systematic range characterization of the 239-242 cluster.
Still missing
- The exact p.Trp239Cys substitution was not individually tested in the Boudeau study
- evidence is from cluster-level characterization. A second independent functional study would strengthen to strong level.
Sources
PS4 SupportingThe variant NM_000455.4:c.717G>C (p.Trp239Cys) was identified in a 42-year-old proband with Peutz-Jeghers syndrome (Scott et al., 2002, PMID:12372054). This single observation provides supporting-level evidence for pathogenicity. Details ▾Hide ▴
Evidence considered
- One PJS proband harboring c.717G>C (p.Trp239Cys) reported in PMID:12372054 (Scott et al. 2002). Variant was absent from 50 control individuals.
Still missing
- Only one clinically documented case identified
- additional proband observations would strengthen this criterion.
Sources
PM1 ModerateThe p.Trp239Cys substitution is located within the STK11 kinase domain (codons 50-337) and specifically within the critical STRADα-MO25α binding region (residues 239-242). Functional studies by Boudeau et al. (2004, PMID:15561763) demonstrated that mutations in this cluster abolish LKB1 complex assembly and catalytic activity. Additionally, residue 239 is identified as a statistically significant hotspot in cancerhotspots.org. Details ▾Hide ▴
Evidence considered
- STK11 kinase domain (codons 50-337)
- residue 239 within the 239-242 STRADα-binding cluster shown to be critical for LKB1 function (PMID:15561763)
- statistically significant hotspot at cancerhotspots.org.
Sources
PM2 SupportingThis variant is absent from gnomAD v2.1 (exomes), gnomAD v4.1 (exomes/genomes), and gnomAD-Canada v1.0, meeting the PM2 threshold for rare variant absent from population databases (allele frequency < 0.1%). Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1
- absent from gnomAD v4.1
- absent from gnomAD-Canada v1.0.
Sources
PP2 SupportingSTK11 is a well-established tumor suppressor gene in which missense variants are a recognized mechanism of disease. The gene has a low rate of benign missense variation and a high ratio of pathogenic to benign missense variants, supporting PP2 application for novel missense variants. Details ▾Hide ▴
Evidence considered
- STK11 is a tumor suppressor with a high proportion of pathogenic missense variants relative to benign variants
- Peutz-Jeghers syndrome is primarily caused by LoF variants including missense substitutions in the kinase domain.
Sources
PP3 SupportingREVEL predicts a damaging effect with a score of 0.859. SpliceAI predicts no significant splice impact (max delta score 0.15). BayesDel score is 0.484. Multiple lines of in silico evidence support a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL score 0.859 (damaging)
- BayesDel score 0.484
- SpliceAI max delta 0.15 (no significant splice impact). Multiple in silico predictors support a deleterious effect on protein function.
Sources
PP4 SupportingThe variant was identified in a patient with clinically confirmed Peutz-Jeghers syndrome (hamartomatous polyposis, mucocutaneous pigmentation), a phenotype highly specific for STK11. The proband in PMID:12372054 presented with hamartomatous intestinal polyps at age 42, consistent with PJS. Details ▾Hide ▴
Evidence considered
- PJS phenotype in proband (PMID:12372054): hamartomatous polyposis
- diagnosed at age 42. PJS is a highly specific phenotype for STK11 pathogenic variants.
Sources
PP5 SupportingThis variant has been reported as Pathogenic in ClinVar (variation ID 7458) by a clinical testing laboratory (Labcorp/Invitae), with criteria provided. Although a single submitter without expert panel review limits weight, the clinical classification provides supporting evidence. Details ▾Hide ▴
Evidence considered
- ClinVar variation ID 7458: Pathogenic classification by Labcorp Genetics (Invitae)
- criteria provided
- single submitter. One clinical laboratory classification.
Sources
Not met · 12 · evaluated, threshold not reached
PS1 No evidence was identified that a different nucleotide change at this position produces the same amino acid change (p.Trp239Cys) and has been classified as pathogenic. The only reported variant at codon 239 is p.Trp239Gly (c.715T>G) in PMID:20497868, which results in a different amino acid substitution. Details ▾Hide ▴
Evidence considered
- Sister variant at codon 239 (p.Trp239Gly) reported in PMID:20497868 is a different amino acid substitution
- does not satisfy PS1 which requires same amino acid change from a different nucleotide.
Sources
PM5 A different missense variant at the same codon (p.Trp239Gly, c.715T>G) was reported in a PJS patient by Weng et al. (2010, PMID:20497868), but was classified as a variant of unknown significance. No clearly established pathogenic missense variant at codon 239 with a different amino acid substitution was identified to satisfy PM5 criteria. Details ▾Hide ▴
Evidence considered
- Sister missense variant p.Trp239Gly (c.715T>G) at same codon reported as variant of unknown significance in PMID:20497868
- does not meet PM5 threshold requiring an established pathogenic missense change at the same residue.
Sources
BA1 This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. The allele frequency does not exceed the BA1 threshold of 1%. Details ▾Hide ▴
Evidence considered
- Variant absent from all population databases
- allele frequency is 0%.
Sources
BS1 This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. The allele frequency does not exceed the BS1 threshold of 0.3%. Details ▾Hide ▴
Evidence considered
- Variant absent from all population databases
- allele frequency is 0%.
Sources
BS2 No evidence that this variant has been observed in healthy adult controls in the absence of disease. The variant is absent from gnomAD and was not found in 50 control individuals tested in PMID:12372054. Details ▾Hide ▴
Evidence considered
- Variant not observed in healthy population controls
- absent from gnomAD and absent from 50 control individuals tested in PMID:12372054.
Sources
BS3 Functional studies do not show a benign effect. Boudeau et al. (2004, PMID:15561763) demonstrated that mutations in the 239-242 cluster abolish STRADα-MO25α binding and catalytic activity, consistent with a loss-of-function mechanism. No well-established functional studies support a benign interpretation. Details ▾Hide ▴
Evidence considered
- Functional evidence from PMID:15561763 shows damaging effect (loss of STRADα binding and catalytic activity for 239-242 cluster mutants)
- no benign functional data identified.
Sources
BS4 No segregation data are available to assess whether the variant fails to segregate with disease. No non-segregation evidence was identified. Details ▾Hide ▴
Still missing
- No segregation data available.
BP1 BP1 applies when a missense variant is found in a gene where only truncating variants cause disease. STK11 has numerous well-documented pathogenic missense variants associated with Peutz-Jeghers syndrome, so BP1 does not apply. Details ▾Hide ▴
Evidence considered
- STK11 has many established pathogenic missense variants causing PJS
- BP1 is inapplicable.
Sources
BP2 No evidence that this variant has been observed in trans with a known pathogenic STK11 variant. No data are available to assess BP2. Details ▾Hide ▴
Still missing
- No trans configuration data available.
BP4 Multiple in silico predictors suggest a damaging effect. REVEL score is 0.859 (damaging). There is no in silico evidence supporting a benign interpretation. Details ▾Hide ▴
Evidence considered
- REVEL 0.859 (damaging
- not benign)
- BayesDel 0.484
- no benign in silico prediction identified.
Sources
revelbayesdel
BP5 No evidence that an alternate molecular basis for disease has been identified in a case where this variant was found. No data available to assess BP5. Details ▾Hide ▴
Still missing
- No alternate molecular cause data available.
BP6 This variant has been classified as Pathogenic, not benign, in ClinVar (variation ID 7458). BP6 requires a reputable source to classify the variant as benign or likely benign. Details ▾Hide ▴
Evidence considered
- ClinVar classification is Pathogenic
- BP6 requires benign/likely benign classification.
Sources
Not assessed · 4 · no assessment recorded
PS2 No de novo data are available for this variant. Neither the clinical literature nor ClinVar submissions report confirmed de novo occurrence with parental testing. Details ▾Hide ▴
Still missing
- Absence of de novo testing data
- parental genotypes not available for the proband in PMID:12372054.
PM6 No de novo data are available for this variant. No confirmed reports of de novo occurrence with confirmed maternity and paternity testing were identified. Details ▾Hide ▴
Still missing
- Absence of de novo testing data.
PP1 No segregation data are available for this variant. The proband in PMID:12372054 was a single case without reported family segregation analysis. Details ▾Hide ▴
Still missing
- No co-segregation data available.
PS5 PS5 (two or more independent occurrences of a novel variant in affected individuals with a consistent phenotype in the absence of a known pathogenic variant in the gene) is not applicable here. This variant has been reported in ClinVar and in the literature. Formal PS5 counting was not pursued as stronger evidence streams are available. Details ▾Hide ▴
No further detail was recorded.
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis is a missense variant (p.Trp239Cys), not a null variant (nonsense, frameshift, or canonical ±1,2 splice site). The generic PVS1 framework does not apply to missense substitutions. Details ▾Hide ▴
Evidence considered
- Missense variant (c.717G>C
- p.Trp239Cys)
- variant bucket: other
- pvs1_gene_context confirms STK11 LoF mechanism is eligible but variant does not meet null-variant criteria per ClinGen SVI PVS1 recommendations (PMC6185798).
Sources
PM3 N/ASTK11-associated Peutz-Jeghers syndrome is an autosomal dominant disorder. PM3 applies to recessive disorders where a variant is detected in trans with a pathogenic variant. Details ▾Hide ▴
No further detail was recorded.
PM4 N/AThis is a single-nucleotide substitution (c.717G>C), not a protein-length-altering variant (non-frameshift indel, stop-loss, or initiation codon change). PM4 assesses variants that change protein length. Details ▾Hide ▴
No further detail was recorded.
BP3 N/AThis is a substitution variant, not an in-frame insertion/deletion. BP3 applies to in-frame indels in non-repeat regions. Details ▾Hide ▴
No further detail was recorded.
BP7 N/AThis is a missense variant (c.717G>C, p.Trp239Cys), not a synonymous variant. BP7 applies only to synonymous variants for which splicing prediction algorithms predict no impact. Details ▾Hide ▴
Evidence considered
- Missense variant (p.Trp239Cys)
- BP7 is for synonymous variants only.
Identifiers
- Gene
- STK11
- Transcript
- NM_000455.4
- Coding (HGVS c.)
- NM_000455.4:c.717G>C
- Protein (HGVS p.)
- NP_000446.1:p.(Trp239Cys)
- GRCh38
- chr19:1220700 G>C
- GRCh37
- chr19:1220699 G>C
- ClinVar
- 7458
Gene diagram
Every interpreted variant in STK11, mapped onto the exon structure of NM_000455.4. Select a row to find it on the plot.
STK11NM_000455.4
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 STK11
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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
- 0.859
- BayesDel
- 0.484
How the predictions were used
PP3 SupportingREVEL predicts a damaging effect with a score of 0.859. SpliceAI predicts no significant splice impact (max delta score 0.15). BayesDel score is 0.484. Multiple lines of in silico evidence support a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL score 0.859 (damaging)
- BayesDel score 0.484
- SpliceAI max delta 0.15 (no significant splice impact). Multiple in silico predictors support a deleterious effect on protein function.
Sources
BP4 Multiple in silico predictors suggest a damaging effect. REVEL score is 0.859 (damaging). There is no in silico evidence supporting a benign interpretation. Details ▾Hide ▴
Evidence considered
- REVEL 0.859 (damaging
- not benign)
- BayesDel 0.484
- no benign in silico prediction identified.
Sources
revelbayesdel
BP7 N/AThis is a missense variant (c.717G>C, p.Trp239Cys), not a synonymous variant. BP7 applies only to synonymous variants for which splicing prediction algorithms predict no impact. Details ▾Hide ▴
Evidence considered
- Missense variant (p.Trp239Cys)
- BP7 is for synonymous variants only.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.15). REVEL score = 0.859. BayesDel score = 0.483857.
9 paper records listed. 2 cited in the classification.
Cited in the classification
-
PMID 12372054 ↗Mutation analysis of the STK11/LKB1 gene and clinical characteristics of an Australian series of Peutz-Jeghers syndrome patients.Scott RJ et al. · 2002 OctScott et al. reported mutation analysis of STK11 in 14 Australian PJS probands. NM_000455.4:c.717G>C (p.Trp239Cys) was identified in a 42-year-old proband (proband 2) with hamartomatous polyposis. The variant was absent from 50 unrelated control individuals and was considered potentially causative though classified as a variant of unknown significance at the time.→ PS4 → PP4 Names this variant
Source detail
A guanine to adenine change in exon 4, which resulted in a tryptophan to cysteine substitution was identified in a 42-year-old patient (proband 2), not previously diagnosed. This substitution was not observed in 50 unrelated individuals and was considered potentially causative.
Location Table 3 (lines 527-530); Results paragraph discussing missense changes (lines 628-643)
-
PMID 15561763 ↗Analysis of the LKB1-STRAD-MO25 complex.Boudeau J et al. · 2004 Dec 15Boudeau et al. systematically characterized 30 LKB1 kinase domain point mutants found in PJS and sporadic cancers using HEK293 co-expression with STRADα and MO25α. Twelve mutants failed to interact with STRADα-MO25α and lost catalytic activity, including a cluster of mutations at residues 239-242. These mutations are in the C-terminal lobe core, likely destabilizing the domain and indirectly preventing STRADα binding. The 19 remaining mutants retained STRADα-MO25α binding with varied activity.→ PS3 → PM1 Names this variant
Source detail
These LKB1 mutants comprised mutations of Leu67 and Phe157, as well as clusters of mutations located between residues 175-182, 239-242 and 297-308.
Location Results, paragraphs 1-2 (Characterisation of mutant forms of LKB1); Discussion, paragraph 1; Figure 1A
Context GST-LKB1 co-expression with Flag-STRADα and Myc-MO25α in HEK293 cells; LKBtide peptide kinase assay; glutathione-Sepharose affinity purification and immunoblotting
Other recorded publications
-
PMID 22980975 ↗Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing.Reports exome and genome sequencing of 183 lung adenocarcinoma tumor/normal pairs, identifying STK11 as a significantly mutated tumor suppressor gene. NM_000455.4:c.717G>C was not identified or reported in this paper.Does not name this variant
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PMID 31712642 ↗Prediction of Deleterious Non-synonymous SNPs of Human STK11 Gene by Combining Algorithms, Molecular Docking, and Molecular Dynamics Simulation.Computational prediction study combining algorithms, molecular docking, and molecular dynamics to identify deleterious non-synonymous SNPs in STK11. NM_000455.4:c.717G>C (p.Trp239Cys) was not specifically analyzed or reported.Does not name this variant
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PMID 17924967 ↗Genetic defects underlying Peutz-Jeghers syndrome (PJS) and exclusion of the polarity-associated MARK/Par1 gene family as potential PJS candidates.de Leng WW et al. · 2007Analyzed LKB1 and MARK gene mutations in 23 PJS families. Identified 21 of 23 (91%) with LKB1 inactivation including point mutations, small indels, and exon deletions. NM_000455.4:c.717G>C was not among the specific mutations reported; the closest reported variant is c.712A>T (p.Ile238Phe) at the adjacent residue.Does not name this variant
Quoted passage
c.712A.T, p.I238F
Table 1 (line 356-490)
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PMID 20497868 ↗Clinical and genetic analysis of Peutz-Jeghers syndrome patients in Taiwan.Weng MT et al. · 2010Weng et al. reported clinical and genetic analysis of 14 Taiwanese PJS patients. A missense mutation at codon 239 was identified in Case 1, but it is NM_000455.4:c.715T>G (p.Trp239Gly), a different nucleotide and amino acid substitution than the queried variant c.717G>C (p.Trp239Cys). The Trp239Gly change was classified as a variant of unknown significance and was not found in 200 control samples.Names this variant
Quoted passage
Case 1 was a missense mutation with a thymine to guanine substitution at base 715 that resulted in a tryptophan to glycine change at codon 239 in exon 5.
Results (Genetic analysis), Table 4, Figure 1A
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PMID 11389158 ↗Peutz-Jeghers families unlinked to STK11/LKB1 gene mutations are highly predisposed to primitive biliary adenocarcinoma.Olschwang S et al. · 2001Analyzed STK11/LKB1 mutations in 34 French PJS families. Identified germline deleterious mutations in 70% of cases and reported that PJS patients without STK11 mutations have elevated risk for proximal biliary adenocarcinoma. NM_000455.4:c.717G>C was not reported among the mutations identified in this cohort.Does not name this variant
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PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.Trepanier A et al. · 2004National Society of Genetic Counselors practice guideline for cancer genetic risk assessment and counseling. Lists Peutz-Jeghers syndrome and its causative gene STK11/LKB1 in a table of rare hereditary cancer syndromes. Does not report or discuss specific STK11 variants.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
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 0.150
Open source ↗
ClinVar
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 ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/7458/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/19-1220699-G-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr19-1220700-G-C?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/19-1220700-G-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000455.4%3Ac.717G…
- OncoKB ↗www.oncokb.org/gene/STK11/W239C
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=STK11+c.717G%3EC
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Pathogenic (1 clinical laboratory). (ClinVarID = 7458)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.15). REVEL score = 0.859. BayesDel score = 0.483857.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant lies in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant lies in a statistically significant hotspot.