About STK11
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
STK11 c.734+17C>G, p.?
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.
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: 1
Benign evidence criteria: 2
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
This variant is present at extremely low frequency in population databases: gnomAD v2.1 allele frequency 0.00227% (6/264,478 alleles), gnomAD v4.1 allele frequency 0.00187% (30/1,600,552 alleles), both well below the 0.1% PM2 threshold.
Benign criteria applied · 2
BP4Supporting
BP4 · supporting
SpliceAI predicts no significant splicing impact for this intronic variant (max delta score = 0.01, well below the 0.1 threshold). Multiple lines of computational evidence suggest no impact on gene product or splicing.
BP6Supporting
BP6 · supporting
This variant has been classified as Likely benign by 4 clinical laboratories (Color Health, Genome-Nilou Lab, Rigshospitalet, Labcorp/Invitae) and Benign by 2 clinical laboratories (GeneDx, KCCC/NGS Laboratory) in ClinVar (Variation ID 379077), all with criteria provided.
Recorded classification: Uncertain significance
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP4 supporting, BP6 supporting; combination = 1 supporting + 2 supporting benign, which maps to VUS because the evidence is conflicting.
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
30 / 1,600,552 alleles
gnomAD v4.1: 30 / 1,600,552 alleles. Recorded AF 1.87435e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.26862e-05; MAF= 0.00227%, 6/264478 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000172073; MAF= 0.01721%, 4/23246 alleles, homozygotes = 0); grpmax FAF= 3.983e-05.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
6 reported laboratory submissions
4 Likely benign · 2 Benign.
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
OncoKB ↗
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Context only
COSMIC ↗
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
29 criteria with recorded statuses: 3 met · 4 not met · 11 not assessed · 11 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000455.5:c.734+17C>G is an intronic variant in STK11 at position +17 of intron 5. No CSPEC/VCEP framework exists for STK11; classification follows generic ACMG/AMP 2015 rules (PMID:25741868).
This variant is present at extremely low frequency in population databases: gnomAD v2.1 allele frequency 0.00227% (6/264,478 alleles) and gnomAD v4.1 allele frequency 0.00187% (30/1,600,552 alleles), with no homozygotes observed (PM2_Supporting).
SpliceAI predicts no significant splicing impact (max delta score = 0.01), and multiple lines of computational evidence suggest no effect on gene product or splicing (BP4_Supporting).
This variant has been independently classified as Likely benign by 4 clinical laboratories and Benign by 2 clinical laboratories in ClinVar (Variation ID 379077), all with criteria provided (BP6_Supporting).
No functional studies, de novo observations, segregation data, or case-control data were identified for this specific variant in the available literature. The 15 PubMed-indexed references associated with this ClinVar entry are practice guidelines and review articles that do not mention NM_000455.5:c.734+17C>G.
Applying generic ACMG/AMP 2015 final combination rules: 1 supporting pathogenic criterion (PM2_Supporting) and 2 supporting benign criteria (BP4_Supporting, BP6_Supporting). With ≥2 supporting benign criteria, this variant is classified as Likely Benign.
No criteria match.
Met · 3
PM2 SupportingThis variant is present at extremely low frequency in population databases: gnomAD v2.1 allele frequency 0.00227% (6/264,478 alleles), gnomAD v4.1 allele frequency 0.00187% (30/1,600,552 alleles), both well below the 0.1% PM2 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF = 0.00227% (6/264
- 478)
- gnomAD v4.1 AF = 0.00187% (30/1
- 600
- 552)
- no homozygotes observed. Absent from gnomAD-Canada v1.0.
Sources
BP4 SupportingSpliceAI predicts no significant splicing impact for this intronic variant (max delta score = 0.01, well below the 0.1 threshold). Multiple lines of computational evidence suggest no impact on gene product or splicing. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01
- no predicted donor/acceptor gain or loss.
Sources
BP6 SupportingThis variant has been classified as Likely benign by 4 clinical laboratories (Color Health, Genome-Nilou Lab, Rigshospitalet, Labcorp/Invitae) and Benign by 2 clinical laboratories (GeneDx, KCCC/NGS Laboratory) in ClinVar (Variation ID 379077), all with criteria provided. Details ▾Hide ▴
Evidence considered
- ClinVar Variation ID 379077: Likely benign (4 clinical labs)
- Benign (2 clinical labs)
- criteria provided
- single submitter each.
Sources
Not met · 4 · evaluated, threshold not reached
PP3 SpliceAI predicts no significant splicing impact (max delta score = 0.01). REVEL and BayesDel scores are not available for this intronic variant. Multiple lines of in silico evidence do not support a deleterious effect. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01 (no predicted splice alteration). REVEL/BayesDel not applicable (intronic). HCI prior not available for STK11.
Sources
PP5 No reputable source has recently reported this variant as pathogenic. ClinVar reports this variant as Likely benign (4 clinical laboratories) and Benign (2 clinical laboratories). Details ▾Hide ▴
Evidence considered
- ClinVar classification: Likely benign/Benign from 6 clinical laboratories (Variation ID 379077).
Sources
BA1 The allele frequency in gnomAD v2.1 (0.00227%) and v4.1 (0.00187%) is far below the 1% BA1 threshold for standing as a benign polymorphism. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF = 0.00227%
- gnomAD v4.1 AF = 0.00187%
- both << 1%.
Sources
BS1 The allele frequency in gnomAD v2.1 (0.00227%) and v4.1 (0.00187%) is far below the 0.3% BS1 threshold. The highest subpopulation frequency (African/African American, 0.02273% in v4.1) also falls below 0.3%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF = 0.00227%
- v4.1 AF = 0.00187%
- grpmax FAF v4.1 = 0.0144%
- all << 0.3%.
Sources
Not assessed · 11 · no assessment recorded
PS2 No de novo evidence identified for this variant. The exploratory literature search did not return usable results, and none of the 15 PubMed-indexed references associated with this ClinVar entry mention NM_000455.5:c.734+17C>G. Details ▾Hide ▴
Still missing
- No de novo observations identified in the literature.
Sources
257418682564557431672839156046282030144323788249253569652539417527854360263895052638921026389258284925323401206835802134
PS3 No functional studies were identified for this specific variant. The ClinVar-associated PMIDs are practice guidelines and review articles, not experimental functional assays. Details ▾Hide ▴
Still missing
- No functional assay data available for this intronic variant.
Sources
257418682564557431672839
PS4 No case-control or case series data were identified for this variant. ClinVar-associated PMIDs are practice guidelines and general review articles that do not report variant-specific prevalence data. Details ▾Hide ▴
Still missing
- No case-control data or enriched case observations for this variant.
Sources
156046282030144323788249253569652539417525645574257418682849253231672839
PM6 No de novo evidence identified. Same assessment as PS2 for this intronic variant. Details ▾Hide ▴
Still missing
- No de novo observations for this variant in the literature.
Sources
257418682564557431672839156046282030144323788249253569652539417527854360263895052638921026389258284925323401206835802134
PP1 No segregation data were identified for this variant in the available literature. Details ▾Hide ▴
Still missing
- No segregation analysis data available.
PP4 No phenotype specificity data are available for this variant. The ClinVar-associated publications are general practice guidelines that do not provide variant-level phenotype data. Details ▾Hide ▴
Still missing
- No variant-specific phenotype data available.
BS2 No specific evidence of this variant observed in healthy adults beyond its presence at low frequency in gnomAD population databases. The variant has been observed in 36 total alleles across gnomAD v2.1 and v4.1 combined, but individual-level phenotype data are not available. Details ▾Hide ▴
Still missing
- No individual-level healthy adult observation data with full penetrance context.
BS3 No well-established functional studies were identified demonstrating no damaging effect for this specific variant. SpliceAI prediction alone (max delta 0.01) is in silico evidence, not a functional assay qualifying for BS3. Details ▾Hide ▴
Still missing
- No functional assay data (e.g.
- splicing reporter assay
- RNA studies) for this variant.
Sources
25741868
BS4 No segregation data are available to assess lack of segregation with disease. Details ▾Hide ▴
Still missing
- No segregation data available for BS4 evaluation.
BP2 No evidence of this variant observed in trans with a known pathogenic STK11 variant was identified in the available literature or databases. Details ▾Hide ▴
Still missing
- No trans-observation data available.
BP5 No evidence was identified of this variant observed in a case with an alternate molecular basis for disease. Details ▾Hide ▴
Still missing
- No alternate-molecular-cause case data available.
Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis intronic variant at position +17 of intron 5 does not fall into PVS1 null-variant buckets (nonsense, frameshift, or canonical ±1,2 splice consensus variants). Per ClinGen SVI PVS1 recommendations (PMC6185798), generic PVS1 framework is not applicable. Details ▾Hide ▴
Evidence considered
- Intronic variant at +17 position
- not a null variant type.
Sources
pvs1_variant_assessmentpvs1_generic_framework ↗
PS1 N/ANo prior pathogenic variant at the same amino acid change exists; this is an intronic variant with no amino acid consequence. Details ▾Hide ▴
Evidence considered
- Intronic variant with no protein change.
PM1 N/AThis is an intronic variant at position +17 of intron 5, not located in a known mutational hotspot or well-characterized critical functional domain. Details ▾Hide ▴
Evidence considered
- Intronic variant
- no hotspot or functional domain location.
PM3 N/ASTK11-related Peutz-Jeghers syndrome is an autosomal dominant condition; PM3 (in trans with pathogenic variant) is not applicable. Details ▾Hide ▴
No further detail was recorded.
PM4 N/AThis is a single-nucleotide substitution, not a protein-length-altering variant (in-frame deletion/insertion, stop-loss, or initiation codon change). Details ▾Hide ▴
No further detail was recorded.
PM5 N/AUnable to confirm classic same-residue PM5 semantics; this is an intronic variant with no amino acid change. No comparator candidates available. Details ▾Hide ▴
Evidence considered
- Intronic variant
- no amino acid residue context for PM5 comparison.
Sources
pm5_candidates
PP2 N/AThis is an intronic variant, not a missense variant. PP2 applies only to missense variants in genes with a low rate of benign missense variation. Details ▾Hide ▴
Evidence considered
- Intronic variant
- PP2 is only applicable to missense variants.
BP1 N/AThis is an intronic variant, not a missense variant. BP1 applies only to missense variants in genes where truncating variants are the primary disease mechanism. Details ▾Hide ▴
Evidence considered
- Intronic variant
- BP1 applies only to missense variants.
BP3 N/AThis is a substitution variant, not an in-frame deletion/insertion in a repetitive region. Details ▾Hide ▴
No further detail was recorded.
BP7 N/AThis is an intronic variant, not a synonymous (silent) variant. BP7 specifically applies to synonymous variants with no predicted splice impact. SpliceAI evidence is captured under BP4. Details ▾Hide ▴
Evidence considered
- Intronic variant
- BP7 is specific to synonymous (coding) variants.
PS5 N/ANo reputable source has recently reported this variant as pathogenic. ClinVar classification is Likely benign/Benign from 6 clinical laboratories. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Likely benign (4 labs) / Benign (2 labs).
Sources
Identifiers
- Gene
- STK11
- Transcript
- NM_000455.5
- Coding (HGVS c.)
- NM_000455.5:c.734+17C>G
- Protein (HGVS p.)
- NP_000446.1:p.?
- GRCh38
- chr19:1220734 C>G
- GRCh37
- chr19:1220733 C>G
- ClinVar
- 379077
Gene diagram
Every interpreted variant in STK11, mapped onto the exon structure of NM_000455.5. Select a row to find it on the plot.
STK11NM_000455.5
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 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
30 / 1,600,552 alleles
AF 1.87e-05 · 0 homozygotes · FAF 0.000144
gnomAD v2.1
6 / 264,478 alleles
AF 2.27e-05 · 0 homozygotes · FAF 3.98e-05
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 1.9e-05 · 30 / 1,600,552 alleles · 0 hom · FAF 0.00014
| African/African American17 / 74,796 | 0.00023 |
| Ashkenazi Jewish1 / 29,062 | 3.4e-05 |
| Remaining individuals2 / 61,708 | 3.2e-05 |
| South Asian1 / 90,096 | 1.1e-05 |
| European (non-Finnish)9 / 1,172,834 | 7.7e-06 |
0 alternate alleles recorded in 5 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern.
gnomAD v2.1
AF 2.3e-05 · 6 / 264,478 alleles · 0 hom · FAF 4e-05
| African/African American4 / 23,246 | 0.00017 |
| Ashkenazi Jewish1 / 9,440 | 0.00011 |
| European (non-Finnish)1 / 117,360 | 8.5e-06 |
0 alternate alleles recorded in 5 other groups: Admixed American, East Asian, European (Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.87435e-05; MAF= 0.00187%, 30/1600552 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000227285; MAF= 0.02273%, 17/74796 alleles, homozygotes = 0); grpmax FAF= 0.00014401.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.26862e-05; MAF= 0.00227%, 6/264478 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000172073; MAF= 0.01721%, 4/23246 alleles, homozygotes = 0); grpmax FAF= 3.983e-05.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingSpliceAI predicts no significant splicing impact for this intronic variant (max delta score = 0.01, well below the 0.1 threshold). Multiple lines of computational evidence suggest no impact on gene product or splicing. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01
- no predicted donor/acceptor gain or loss.
Sources
PP3 SpliceAI predicts no significant splicing impact (max delta score = 0.01). REVEL and BayesDel scores are not available for this intronic variant. Multiple lines of in silico evidence do not support a deleterious effect. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01 (no predicted splice alteration). REVEL/BayesDel not applicable (intronic). HCI prior not available for STK11.
Sources
BP7 N/AThis is an intronic variant, not a synonymous (silent) variant. BP7 specifically applies to synonymous variants with no predicted splice impact. SpliceAI evidence is captured under BP4. Details ▾Hide ▴
Evidence considered
- Intronic variant
- BP7 is specific to synonymous (coding) variants.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
9 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
-
PMID 25645574 ↗ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.Syngal S et al. · 2015No paper-specific finding is recorded.
-
PMID 25741868 ↗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.No paper-specific finding is recorded.
-
PMID 31672839 ↗Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium.No paper-specific finding is recorded.
-
PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.Trepanier A et al. · 2004No paper-specific finding is recorded.
-
PMID 20301443 ↗Peutz-Jeghers Syndrome.Adam MP et al. · 1993No paper-specific finding is recorded.
-
PMID 23788249 ↗ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.Green RC et al. · 2013No paper-specific finding is recorded.
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PMID 25356965 ↗ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.ACMG Board of Directors · 2015No paper-specific finding is recorded.
-
PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015No paper-specific finding is recorded.
-
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
30 / 1,600,552 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
4 Likely benign · 2 Benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/379077/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/19-1220733-C-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr19-1220734-C-G?dataset=gnomad_r4
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000455.5%3Ac.734%…
- OncoKB ↗www.oncokb.org/gene/STK11/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=STK11+c.734+17C%3EG
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.87435e-05; MAF= 0.00187%, 30/1600552 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000227285; MAF= 0.02273%, 17/74796 alleles, homozygotes = 0); grpmax FAF= 0.00014401.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.26862e-05; MAF= 0.00227%, 6/264478 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000172073; MAF= 0.01721%, 4/23246 alleles, homozygotes = 0); grpmax FAF= 3.983e-05.
ClinVar
This variant has been reported in ClinVar as Likely benign (4 clinical laboratories) and as Benign (2 clinical laboratories). (ClinVarID = 379077)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
Somatic
This variant has not previously been reported in somatic cancers (COSMIC).