About STK11
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
STK11 c.920+12C>T, 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: 0
Benign evidence criteria: 1
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
SpliceAI predicts no splicing impact for this intronic variant (max delta score = 0.00). For a variant located at intron position +12 from exon 7, where altered splicing would be the primary plausible disease mechanism, this computational evidence supports a benign interpretation. No other in silico predictors contradict this finding.
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: BP4 supporting; combination = 1 supporting benign, 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
40 / 1,564,668 alleles
gnomAD v4.1: 40 / 1,564,668 alleles. Recorded AF 2.55645e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 5.9476e-05; MAF= 0.00595%, 12/201762 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000453515; MAF= 0.04535%, 8/17640 alleles, homozygotes = 0); grpmax FAF= 0.00036738.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
No listed criterion applied
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
4 reported laboratory submissions
4 Likely benign. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
Context only
ClinVar ↗
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.
26 criteria with recorded statuses: 1 met · 19 not met · 0 not assessed · 6 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.920+12C>T is an intronic variant in STK11 located 12 base pairs downstream of exon 7.
This variant is present in gnomAD at low frequency across multiple populations (0.006% overall in v2.1, 0.003% in v4.1), with the highest subpopulation frequency of 0.046% in the African/African American population, indicating it is a rare but known variant and not absent from population databases.
SpliceAI predicts no splicing impact (max delta score = 0.00), providing computational evidence against a deleterious splicing effect for this intronic variant (BP4_supporting).
ClinVar classifies this variant as Likely benign based on 4 clinical laboratory submissions, though the review status is 1-star (criteria provided, single submitter), which does not reach the expert panel threshold for BP6 application.
No functional studies, de novo reports, segregation data, case-control studies, or variant-specific literature are available for this variant. The variant has not been reported in COSMIC and is not listed as a cancer hotspot.
Based on the available evidence, only BP4 (supporting benign) is met. The overall evidence is insufficient to classify this variant as benign or likely benign; the variant remains a variant of uncertain significance (VUS) with a single supporting benign criterion.
No criteria match.
Met · 1
BP4 SupportingSpliceAI predicts no splicing impact for this intronic variant (max delta score = 0.00). For a variant located at intron position +12 from exon 7, where altered splicing would be the primary plausible disease mechanism, this computational evidence supports a benign interpretation. No other in silico predictors contradict this finding. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score = 0.00 (acceptor gain: null
- acceptor loss: null
- donor gain: null
- donor loss: null)
Still missing
- No REVEL
- BayesDel
- or conservation-based in silico scores available to strengthen BP4 to moderate
Sources
Not met · 19 · evaluated, threshold not reached
PS2 No de novo occurrence data with confirmed parentage is available for this variant. Details ▾Hide ▴
Still missing
- No de novo sequencing data or parentage testing available
PS3 No functional studies have been reported for NM_000455.5:c.920+12C>T. Neither the exact variant nor a systematically characterized range encompassing this intronic position has been functionally assessed in the literature. Details ▾Hide ▴
Still missing
- No functional assay data for this variant or a systematically characterized range that includes it
PS4 No case-control studies or patient cohort data demonstrating enrichment of this variant in affected individuals are available. No publications report this variant in disease-affected individuals. Details ▾Hide ▴
Still missing
- No case-control or cohort data for this variant
PM1 This intronic variant (c.920+12C>T) is not located in a known mutational hotspot or critical functional domain. Cancerhotspots.org identifies no residue-level significance for this position, and the variant lies outside the STK11 protein-coding region. Details ▾Hide ▴
Evidence considered
- Cancerhotspots.org: residue_significant is false
- variant is intronic
- not in a protein domain
PM2 This variant is present in gnomAD at low frequency across multiple populations (12/201,762 alleles in v2.1, AF = 0.006%; 40/1,564,668 alleles in v4.1, AF = 0.003%). While below the 0.1% PM2 threshold, the variant is observed in the African/African American population at 0.046% (34/73,732 alleles in v4.1), indicating it is not absent from population databases and is a known rare variant rather than a novel absent variant. Details ▾Hide ▴
Evidence considered
- Present in gnomAD v2.1 (AC=12
- AN=201
- 762
- AF=0.006%)
- Present in gnomAD v4.1 (AC=40
- AN=1
- 564
- 668
- AF=0.003%)
- Highest subpopulation AF: 0.046% in African/African American (v4.1)
Sources
PM6 No de novo occurrence data (without confirmed parentage) is available for this variant. Details ▾Hide ▴
Still missing
- No de novo reports for this variant
PP1 No co-segregation data with disease in affected family members is available for this variant. Details ▾Hide ▴
Still missing
- No family segregation data
PP3 No in silico prediction tools support a deleterious effect. REVEL and BayesDel scores are unavailable for this non-coding variant, and SpliceAI predicts no splicing impact (max delta score = 0.00). No computational evidence supports pathogenicity. Details ▾Hide ▴
Evidence considered
- REVEL: not found
- BayesDel: not found
- HCI prior: not found
- SpliceAI max delta = 0.00
Sources
PP4 No patient-specific phenotype data or clinical information is available for assessment of this variant. Details ▾Hide ▴
Still missing
- No patient phenotype or clinical data provided
PP5 ClinVar reports this variant as Likely benign with a review status of 'criteria provided, single submitter' (1-star). PP5 requires a reputable source to have classified the variant as pathogenic, which is not the case. The ClinGen expert panel (3-star) threshold required for PP5 application is not met. Details ▾Hide ▴
Evidence considered
- ClinVar classification is Likely benign (review status: 1-star
- not expert panel)
Sources
BA1 The highest observed allele frequency is 0.046% in the African/African American population (gnomAD v4.1), well below the BA1 threshold of 1%. This variant is too rare to be considered a common benign polymorphism. Details ▾Hide ▴
Evidence considered
- Highest subpopulation AF: 0.046% (African/African American
- gnomAD v4.1)
- BA1 threshold: >1%
Sources
BS1 The highest observed allele frequency is 0.046% in the African/African American population (gnomAD v4.1), below the BS1 threshold of 0.3%. The variant is not sufficiently common to apply BS1. Details ▾Hide ▴
Evidence considered
- Highest subpopulation AF: 0.046% (African/African American
- gnomAD v4.1)
- BS1 threshold: >0.3%
Sources
BS2 No data on well-phenotyped healthy adults harboring this variant are available. While the variant is observed in gnomAD (a population database of individuals not selected for disease), the number of observations (12-40 alleles) is insufficient to confidently assert observation in healthy adults with full penetrance expected at an early age for Peutz-Jeghers syndrome. Details ▾Hide ▴
Still missing
- No well-phenotyped healthy adult data for this variant
BS3 No well-established functional studies demonstrating no deleterious effect are available for this variant. SpliceAI predicts no splicing impact (max delta = 0.00), which is evaluated under BP4 rather than BS3. Details ▾Hide ▴
Still missing
- No functional assay data demonstrating no deleterious effect
BS4 No segregation data are available to demonstrate lack of co-segregation with disease in affected families. Details ▾Hide ▴
Still missing
- No segregation data for non-segregation analysis
BP2 No data on observation of this variant in trans with a known pathogenic variant in a recessive disorder are available. STK11-related Peutz-Jeghers syndrome is autosomal dominant, further limiting BP2 applicability. Details ▾Hide ▴
Still missing
- No trans observation data
BP5 No cases have been reported in which this variant is found in a patient with an alternate molecular basis for disease. Details ▾Hide ▴
Still missing
- No data on cases with alternate molecular diagnosis
BP6 ClinVar classifies this variant as Likely benign based on 4 clinical laboratory submissions (GeneDx, Mendelics, Color Health, Invitae), but the review status is 'criteria provided, single submitter' (1-star). This does not meet the 3-star expert panel threshold required for BP6 application at supporting strength. Details ▾Hide ▴
Evidence considered
- ClinVar Likely benign classification from 4 clinical labs
- 1-star review status
Still missing
- No expert panel review of this variant
Sources
PS5 ClinVar reports this variant as Likely benign, not pathogenic. No reputable source has classified this variant as pathogenic. Details ▾Hide ▴
Evidence considered
- ClinVar classification is Likely benign (4 clinical laboratories
- 1-star review status)
Sources
Not applicable · 6· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis intronic variant (c.920+12C>T) does not fall into the default null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants, and SpliceAI predicts no splicing impact (max delta = 0.00). PVS1 is not applicable. Details ▾Hide ▴
Evidence considered
- Variant class is intronic (+12) with no predicted splicing effect per SpliceAI
Sources
PS1 N/AThis intronic variant does not alter the coding sequence; PS1 requires an established pathogenic variant producing the same amino acid change, which is not applicable for a non-coding variant. Details ▾Hide ▴
Evidence considered
- Intronic variant with no amino acid change
PM5 N/AThis intronic variant has no predicted protein consequence (NP_000446.1:p.?); PM5 requires a different missense change at the same residue previously classified as pathogenic, which cannot be assessed for a non-coding variant. Details ▾Hide ▴
Evidence considered
- pm5_candidates confirms eligible_for_classic_pm5_search is false
- no same-residue comparators available
Sources
pm5_candidates
PP2 N/APP2 applies to missense variants in genes with a low rate of benign missense variation; this is an intronic variant and does not meet the criterion scope. Details ▾Hide ▴
Evidence considered
- Intronic variant
- not a missense variant
BP1 N/ABP1 applies to missense variants in genes where primarily truncating variants cause disease; this is an intronic variant and does not fall within BP1 scope. Details ▾Hide ▴
Evidence considered
- Intronic variant
- not a missense variant
BP7 N/ABP7 applies to synonymous (silent) variants for which splicing algorithms predict no impact to the splice consensus sequence; this is an intronic variant, not a synonymous coding variant. Details ▾Hide ▴
Evidence considered
- Intronic variant
- not a synonymous coding variant
Identifiers
- Gene
- STK11
- Transcript
- NM_000455.5
- Coding (HGVS c.)
- NM_000455.5:c.920+12C>T
- Protein (HGVS p.)
- NP_000446.1:p.?
- GRCh38
- chr19:1222018 C>T
- GRCh37
- chr19:1222017 C>T
- ClinVar
- 234418
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
40 / 1,564,668 alleles
AF 2.56e-05 · 0 homozygotes · FAF 0.000339
gnomAD v2.1
12 / 201,762 alleles
AF 5.95e-05 · 0 homozygotes · FAF 0.000367
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 2.6e-05 · 40 / 1,564,668 alleles · 0 hom · FAF 0.00034
| African/African American34 / 73,732 | 0.00046 |
| Admixed American3 / 53,118 | 5.6e-05 |
| Remaining individuals1 / 60,600 | 1.7e-05 |
| South Asian1 / 85,050 | 1.2e-05 |
| European (non-Finnish)1 / 1,155,394 | 8.7e-07 |
0 alternate alleles recorded in 5 other groups: European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 5.9e-05 · 12 / 201,762 alleles · 0 hom · FAF 0.00037
| African/African American8 / 17,640 | 0.00045 |
| Remaining individuals1 / 5,728 | 0.00017 |
| Admixed American2 / 27,396 | 7.3e-05 |
| European (non-Finnish)1 / 85,128 | 1.2e-05 |
0 alternate alleles recorded in 4 other groups: Ashkenazi Jewish, East Asian, European (Finnish), South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 2.55645e-05; MAF= 0.00256%, 40/1564668 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000461129; MAF= 0.04611%, 34/73732 alleles, homozygotes = 0); grpmax FAF= 0.00033884.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 5.9476e-05; MAF= 0.00595%, 12/201762 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000453515; MAF= 0.04535%, 8/17640 alleles, homozygotes = 0); grpmax FAF= 0.00036738.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingSpliceAI predicts no splicing impact for this intronic variant (max delta score = 0.00). For a variant located at intron position +12 from exon 7, where altered splicing would be the primary plausible disease mechanism, this computational evidence supports a benign interpretation. No other in silico predictors contradict this finding. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score = 0.00 (acceptor gain: null
- acceptor loss: null
- donor gain: null
- donor loss: null)
Still missing
- No REVEL
- BayesDel
- or conservation-based in silico scores available to strengthen BP4 to moderate
Sources
PP3 No in silico prediction tools support a deleterious effect. REVEL and BayesDel scores are unavailable for this non-coding variant, and SpliceAI predicts no splicing impact (max delta score = 0.00). No computational evidence supports pathogenicity. Details ▾Hide ▴
Evidence considered
- REVEL: not found
- BayesDel: not found
- HCI prior: not found
- SpliceAI max delta = 0.00
Sources
BP7 N/ABP7 applies to synonymous (silent) variants for which splicing algorithms predict no impact to the splice consensus sequence; this is an intronic variant, not a synonymous coding variant. Details ▾Hide ▴
Evidence considered
- Intronic variant
- not a synonymous coding variant
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
7 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
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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.ACMG/AMP consensus standards and guidelines for the interpretation of sequence variants. This publication defines the variant classification framework and criteria but does not discuss or evaluate any specific STK11 variants.Does not name this variant
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PMID 31672839 ↗Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium.Updated consensus recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium for managing individuals at increased risk for familial pancreatic cancer. STK11 is listed among genes (Peutz-Jeghers syndrome) for which pancreatic surveillance is recommended, but no specific STK11 variants are discussed.Does not name this variant
Quoted passage
Surveillance for CDKN2A and STK11 (Peutz-Jegher syndrome) mutation carriers is recommended irrespective of patients' family history of pancreatic cancer, because of their high lifetime risk.
Results section, germline mutation carriers paragraph; STK11 mentioned as a gene for which surveillance is recommended
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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 recommendations for cancer genetic risk assessment and counseling. Discusses general principles of cancer genetic counseling; no specific STK11 variants are evaluated.Does not name this variant
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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 · 2015ACMG policy statement on updated recommendations for analysis and reporting of secondary findings in clinical genome-scale sequencing. A policy document that does not evaluate specific variants.Does not name this variant
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PMID 26389210 ↗Genetics of Breast and Gynecologic Cancers (PDQ®): Health Professional Version.PDQ Cancer Genetics Editorial Board · 2002PDQ cancer genetics summary on the genetics of breast and gynecologic cancers. Provides general cancer genetics information; no specific STK11 variants are discussed.Does not name this variant
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PMID 26389505 ↗Genetics of Colorectal Cancer (PDQ®): Health Professional Version.PDQ Cancer Genetics Editorial Board · 2002PDQ cancer genetics summary on the genetics of colorectal cancer. Discusses hereditary colorectal cancer syndromes at the gene level; no specific STK11 variants are evaluated.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Sherloc comprehensive refinement of ACMG-AMP variant classification criteria. A methods paper that defines classification rules; no specific STK11 variants are discussed or evaluated.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
40 / 1,564,668 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
4 Likely benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/234418/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/19-1222017-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr19-1222018-C-T?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/19-1222018-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000455.5%3Ac.920%…
- OncoKB ↗www.oncokb.org/gene/STK11/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=STK11+c.920+12C%3ET
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= 2.55645e-05; MAF= 0.00256%, 40/1564668 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000461129; MAF= 0.04611%, 34/73732 alleles, homozygotes = 0); grpmax FAF= 0.00033884.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 5.9476e-05; MAF= 0.00595%, 12/201762 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000453515; MAF= 0.04535%, 8/17640 alleles, homozygotes = 0); grpmax FAF= 0.00036738.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Likely benign (4 clinical laboratories). (ClinVarID = 234418)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Somatic
This variant has not previously been reported in somatic cancers (COSMIC).