About STK11
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
STK11 c.1226G>A, p.(Arg409Gln)
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: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
NM_000455.5:c.1226G>A is present in gnomAD v2.1 at an allele frequency of 0.0036% (7/193,536 alleles, 0 homozygotes) and in gnomAD v4.1 at 0.0033% (52/1,587,284 alleles, 0 homozygotes), well below the 0.1% threshold for PM2 at supporting level. Absent from gnomAD-Canada.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.122 (well below the 0.5 pathogenic cutoff), BayesDel score is -0.514 (strongly in the benign range), and SpliceAI predicts no aberrant splicing (max delta = 0.00). All three independent in silico predictors concur that this variant is likely benign.
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; combination = 1 supporting + 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
52 / 1,587,284 alleles
gnomAD v4.1: 52 / 1,587,284 alleles. Recorded AF 3.27604e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.6169e-05; MAF= 0.00362%, 7/193536 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000198649; MAF= 0.01986%, 1/5034 alleles, homozygotes = 0); grpmax FAF= 2.36e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0001086130118388183, 2/18414 alleles, homozygotes = 0).
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
15 reported laboratory submissions
11 Uncertain significance · 2 Likely benign · 1 Uncertain Significance · 1 Benign. ClinVar API review status: criteria provided, conflicting classifications.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. STK11, a tumor suppressor and intracellular kinase, is frequently mutated in lung cancer.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV53071079, n = 1 times).
Cancer Hotspots
This variant does not lie 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.
26 criteria with recorded statuses: 2 met · 23 not met · 0 not assessed · 1 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.1226G>A (p.Arg409Gln) is a missense variant in STK11, a gene associated with autosomal dominant Peutz-Jeghers syndrome.
This variant is present at extremely low frequency in population databases: gnomAD v2.1 allele frequency 0.0036% (7/193,536 alleles) and gnomAD v4.1 allele frequency 0.0033% (52/1,587,284 alleles), with no homozygotes observed. PM2 (supporting) is met.
Multiple computational prediction tools suggest a benign effect: REVEL score 0.122, BayesDel score -0.514, and SpliceAI max delta 0.00. BP4 (supporting) is met.
A same-residue variant, p.Arg409Trp (R409W), was evaluated in a functional study (PMID:34849607) and was found to retain WT-like kinase activity and p53-mediated transcriptional activation, suggesting that amino acid substitution at this position may not disrupt STK11 function.
The variant has been reported in ClinVar predominantly as a variant of uncertain significance (11 clinical laboratories), with 2 laboratories classifying as likely benign and 1 as benign. No expert panel review is available.
This variant is observed in COSMIC in somatic cancers at low frequency (n=1), which does not provide evidence for germline pathogenicity.
No variant-specific publications were identified in the reviewed literature. PMID:34849607 evaluated R409W at the same residue but did not directly study R409Q.
Applying generic ACMG/AMP 2015 classification rules: one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4) are met. These offset each other, resulting in an overall classification of Uncertain Significance.
No criteria match.
Met · 2
PM2 SupportingNM_000455.5:c.1226G>A is present in gnomAD v2.1 at an allele frequency of 0.0036% (7/193,536 alleles, 0 homozygotes) and in gnomAD v4.1 at 0.0033% (52/1,587,284 alleles, 0 homozygotes), well below the 0.1% threshold for PM2 at supporting level. Absent from gnomAD-Canada. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF = 0.0036% (7/193
- 536 alleles)
- <0.1% threshold
- gnomAD v4.1 AF = 0.0033% (52/1
- 587
- 284 alleles)
- Absent from gnomAD-Canada v1.0
- No homozygotes observed in any population database
Sources
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.122 (well below the 0.5 pathogenic cutoff), BayesDel score is -0.514 (strongly in the benign range), and SpliceAI predicts no aberrant splicing (max delta = 0.00). All three independent in silico predictors concur that this variant is likely benign. Details ▾Hide ▴
Evidence considered
- REVEL = 0.122 (below 0.5 pathogenic threshold
- favors benign)
- BayesDel noAF = -0.514 (benign range
- below -0.18 threshold)
- SpliceAI max delta = 0.00 (no predicted splicing impact)
Sources
Not met · 23 · evaluated, threshold not reached
PS1 No known pathogenic variant has been reported at the same nucleotide position (c.1226G>A) with the same amino acid change. No evidence from ClinVar, COSMIC, or literature supports a PS1-level prior. Details ▾Hide ▴
Evidence considered
- No pathogenic variant at this exact nucleotide position identified in ClinVar or COSMIC.
Sources
PS2 No de novo occurrence of NM_000455.5:c.1226G>A was identified in any reviewed publication or ClinVar submission. No parentage-confirmed de novo report available. Details ▾Hide ▴
Evidence considered
- No de novo evidence identified in literature or ClinVar submissions.
PS3 No well-established functional study directly assessing NM_000455.5:c.1226G>A (p.Arg409Gln) was identified. PMID:34849607 evaluated the same-residue variant p.Arg409Trp and found it retained WT-like kinase activity and p53-mediated transcriptional activation, but this does not constitute direct functional evidence for p.Arg409Gln. Details ▾Hide ▴
Evidence considered
- Functional data exist for same-residue variant R409W (WT-like function) but not for R409Q directly.
Still missing
- No direct functional assay data for p.Arg409Gln.
Sources
PS4 No case-control study demonstrates statistically significant enrichment of NM_000455.5:c.1226G>A in affected individuals versus controls. The variant has been observed in gnomAD population databases at low frequency (0.0036%), which does not support a PS4 argument. Details ▾Hide ▴
Evidence considered
- Variant present in general population at very low frequency
- no case-control enrichment data available.
Still missing
- No published case-control data for this variant.
Sources
PM1 The variant does not lie in a statistically significant mutational hotspot in STK11. Hotspot analysis of the residue (R409) did not identify significant clustering of pathogenic variants. Details ▾Hide ▴
Evidence considered
- Residue R409 is not within a statistically significant hotspot region of STK11.
PM5 PM5 candidate harvesting did not identify a confirmed pathogenic missense variant at the same residue (R409) suitable as a comparator. R409W was evaluated in PMID:34849607 and found to retain WT-like kinase and transcriptional activity, precluding its use as a pathogenic comparator for PM5. Details ▾Hide ▴
Evidence considered
- PM5 candidate harvesting found no pathogenic same-residue comparator
- R409W (same residue) studied in PMID:34849607: WT-like function
- not a pathogenic comparator
Sources
pm5_candidatesPMID:34849607 ↗
PM6 No confirmed de novo occurrence of NM_000455.5:c.1226G>A has been reported. PM6 requires a de novo observation with confirmed maternity and paternity, which is not available. Details ▾Hide ▴
Evidence considered
- No de novo report identified.
PP1 No segregation data are available for NM_000455.5:c.1226G>A. No family studies demonstrating co-segregation with disease have been published. Details ▾Hide ▴
Evidence considered
- No segregation data available.
Still missing
- No family segregation studies identified.
PP2 PP2 applies when a missense variant occurs in a gene with a low rate of benign missense variation and where missense variants are a common mechanism of disease. STK11 has a significant number of benign missense variants reported and the specific variant has been observed in population databases, so PP2 is not met. Details ▾Hide ▴
Evidence considered
- STK11 missense variants are not uniformly pathogenic
- benign missense variation exists.
Sources
PP3 Multiple lines of computational evidence suggest a benign effect rather than a deleterious effect. REVEL score is 0.122 (well below typical pathogenic threshold of >0.5), BayesDel score is -0.514 (strongly in the benign range), and SpliceAI predicts no splicing impact (max delta = 0.00). These results are discordant with a PP3 determination. Details ▾Hide ▴
Evidence considered
- REVEL = 0.122 (below 0.5 pathogenic threshold)
- BayesDel noAF = -0.514 (benign range)
- SpliceAI max delta = 0.00 (no predicted splice impact)
Sources
PP4 No detailed phenotypic data specific to individuals carrying NM_000455.5:c.1226G>A are available. PP4 requires that the variant be identified in a patient with a phenotype highly specific for the gene/disease, which cannot be assessed. Details ▾Hide ▴
Evidence considered
- No patient-level phenotypic data available for this variant.
Still missing
- No phenotype-specific case data available.
PP5 No reputable source (expert panel, professional practice guideline, or clinical diagnostic laboratory with comprehensive evidence) classifies NM_000455.5:c.1226G>A as pathogenic. ClinVar classification is VUS (11 labs) with minority likely benign/benign (3 labs); no expert panel review exists. Details ▾Hide ▴
Evidence considered
- ClinVar classification: VUS (11 labs)
- Likely benign (2 labs)
- Benign (1 lab)
- No expert panel review available
- No practice guideline reports variant as pathogenic
Sources
BA1 The variant allele frequency in gnomAD (0.0036% v2.1, 0.0033% v4.1) is far below the BA1 threshold of >1% in any population. BA1 is not met. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF = 0.0036%
- <1% BA1 threshold
- gnomAD v4.1 AF = 0.0033%
- Highest subpopulation AF = 0.0199% (Remaining individuals)
- <1%
Sources
BS1 The variant allele frequency in gnomAD (0.0036% v2.1, 0.0033% v4.1) is well below the BS1 threshold of >0.3% in any population. BS1 is not met. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF = 0.0036%
- <0.3% BS1 threshold
- gnomAD v4.1 AF = 0.0033%
Sources
BS2 No homozygous observations of NM_000455.5:c.1226G>A have been reported in any population database. BS2 requires observation in a healthy adult individual in trans with a pathogenic variant or in a homozygous state, which is not available. Details ▾Hide ▴
Evidence considered
- No homozygotes observed in gnomAD v2.1 or v4.1.
Still missing
- No homozygous or compound heterozygous observations available.
Sources
BS3 No well-established functional study directly demonstrates that NM_000455.5:c.1226G>A (p.Arg409Gln) has no deleterious effect. A same-residue variant (p.Arg409Trp) was shown to retain WT-like function in PMID:34849607, but this indirect evidence alone is insufficient to meet BS3 without direct testing of p.Arg409Gln. Details ▾Hide ▴
Evidence considered
- R409W (same residue) retained WT-like kinase activity and p53 transcriptional activation in PMID:34849607
- No direct functional testing of R409Q available
Still missing
- No direct functional assay for p.Arg409Gln.
Sources
BS4 No segregation data are available to demonstrate lack of co-segregation with disease. BS4 requires non-segregation evidence, which has not been reported for this variant. Details ▾Hide ▴
Evidence considered
- No segregation or non-segregation data available.
Still missing
- No family segregation data.
BP1 BP1 applies when a missense variant occurs in a gene where only truncating variants cause disease. STK11 is associated with Peutz-Jeghers syndrome through both missense and truncating pathogenic variants; therefore BP1 does not apply. Details ▾Hide ▴
Evidence considered
- STK11 disease mechanism includes both missense and truncating pathogenic variants.
Sources
pvs1_gene_context
BP2 No observation of NM_000455.5:c.1226G>A occurring in trans with a known pathogenic STK11 variant has been reported. BP2 requires co-occurrence data that is not available. Details ▾Hide ▴
Evidence considered
- No co-occurrence data with pathogenic STK11 variants available.
Still missing
- No co-occurrence observations.
BP5 BP5 requires that the variant be found in a case with an alternate molecular basis for disease. No such case data are available for NM_000455.5:c.1226G>A. Details ▾Hide ▴
Evidence considered
- No case-level data with an alternate molecular cause in a variant carrier.
Still missing
- No case with alternate molecular diagnosis available.
BP6 While two clinical laboratories classify NM_000455.5:c.1226G>A as likely benign and one as benign in ClinVar, these are minority opinions (3 of 16 submissions) and no expert panel or reputable source with comprehensive evidence supports a benign classification. ClinVar consensus remains VUS. BP6 is not met. Details ▾Hide ▴
Evidence considered
- ClinVar: 2 labs classify as Likely benign
- 1 as Benign (minority)
- Majority VUS
- no expert panel review supporting benign classification
Sources
BP7 BP7 applies to synonymous variants with no predicted splice impact. NM_000455.5:c.1226G>A is a missense variant, not a synonymous variant. BP7 does not apply. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 criteria are specific to synonymous variants.
PS5 No evidence that NM_000455.5:c.1226G>A has been identified in a case where an alternate molecular cause of disease was established. No data to support this criterion. Details ▾Hide ▴
Evidence considered
- No case-level data identifying an alternate molecular cause in a proband carrying this variant.
Still missing
- No case data with alternate molecular diagnosis available.
Not applicable · 1· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_000455.5:c.1226G>A is a missense variant (p.Arg409Gln) and does not fall into the default generic PVS1 null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants. PVS1 is not applicable. Details ▾Hide ▴
Evidence considered
- Missense substitution
- not a null variant.
Sources
pvs1_variant_assessment
Identifiers
- Gene
- STK11
- Transcript
- NM_000455.5
- Coding (HGVS c.)
- NM_000455.5:c.1226G>A
- Protein (HGVS p.)
- NP_000446.1:p.(Arg409Gln)
- GRCh38
- chr19:1226571 G>A
- GRCh37
- chr19:1226570 G>A
- ClinVar
- 142292
- COSMIC
- COSV53071079
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
52 / 1,587,284 alleles
AF 3.28e-05 · 0 homozygotes · FAF 3.1e-05
gnomAD v2.1
7 / 193,536 alleles
AF 3.62e-05 · 0 homozygotes · FAF 2.36e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 3.3e-05 · 52 / 1,587,284 alleles · 0 hom · FAF 3.1e-05
| African/African American3 / 74,264 | 4e-05 |
| European (non-Finnish)47 / 1,168,440 | 4e-05 |
| East Asian1 / 43,246 | 2.3e-05 |
| Remaining individuals1 / 61,366 | 1.6e-05 |
0 alternate alleles recorded in 6 other groups: Admixed American, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 3.6e-05 · 7 / 193,536 alleles · 0 hom · FAF 2.4e-05
| Remaining individuals1 / 5,034 | 0.0002 |
| European (non-Finnish)5 / 82,982 | 6e-05 |
| Admixed American1 / 29,352 | 3.4e-05 |
0 alternate alleles recorded in 5 other groups: African/African American, Ashkenazi Jewish, East Asian, European (Finnish), South Asian.
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 3.27604e-05; MAF= 0.00328%, 52/1587284 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 4.03964e-05; MAF= 0.00404%, 3/74264 alleles, homozygotes = 0); grpmax FAF= 3.099e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.6169e-05; MAF= 0.00362%, 7/193536 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000198649; MAF= 0.01986%, 1/5034 alleles, homozygotes = 0); grpmax FAF= 2.36e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0001086130118388183, 2/18414 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.122
- BayesDel
- -0.514
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.122 (well below the 0.5 pathogenic cutoff), BayesDel score is -0.514 (strongly in the benign range), and SpliceAI predicts no aberrant splicing (max delta = 0.00). All three independent in silico predictors concur that this variant is likely benign. Details ▾Hide ▴
Evidence considered
- REVEL = 0.122 (below 0.5 pathogenic threshold
- favors benign)
- BayesDel noAF = -0.514 (benign range
- below -0.18 threshold)
- SpliceAI max delta = 0.00 (no predicted splicing impact)
Sources
PP3 Multiple lines of computational evidence suggest a benign effect rather than a deleterious effect. REVEL score is 0.122 (well below typical pathogenic threshold of >0.5), BayesDel score is -0.514 (strongly in the benign range), and SpliceAI predicts no splicing impact (max delta = 0.00). These results are discordant with a PP3 determination. Details ▾Hide ▴
Evidence considered
- REVEL = 0.122 (below 0.5 pathogenic threshold)
- BayesDel noAF = -0.514 (benign range)
- SpliceAI max delta = 0.00 (no predicted splice impact)
Sources
BP7 BP7 applies to synonymous variants with no predicted splice impact. NM_000455.5:c.1226G>A is a missense variant, not a synonymous variant. BP7 does not apply. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 criteria are specific to synonymous variants.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.122. BayesDel score = -0.513561.
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
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PMID 17676035 ↗LKB1 modulates lung cancer differentiation and metastasis.Demonstrated that LKB1 (STK11) loss cooperates with oncogenic Kras in mouse lung cancer models, promoting metastasis and expanded histological spectrum. Gene-level study; NM_000455.5:c.1226G>A was not mentioned.Does not name this variant
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PMID 34849607 ↗Functional assessment of somatic STK11 variants identified in primary human non-small cell lung cancers.Evaluated 28 STK11 missense variants using autophosphorylation kinase assay and p53-mediated luciferase reporter assay in A549 cells. The same-residue variant R409W (p.Arg409Trp) retained WT-like kinase activity and p53-mediated transcriptional activation, suggesting amino acid substitution at position 409 does not ablate function. NM_000455.5:c.1226G>A (p.Arg409Gln) was not directly tested.Does not name this variant
Quoted passage
In all, 13/28 variants (S31F, R104G, Q112E, G155R, H202R, R221Q, P275L, P280A, K311N, F354L, A397S, R409W, A417S) were found to retain autophosphorylation activity under the conditions employed in our in vitro kinase assay
Table 1 (variant list), Figures 5B-D (functional results)
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PMID 24033266 ↗A systematic approach to assessing the clinical significance of genetic variants.Described a systematic variant assessment tool (VAT) for clinical significance classification. Methodology paper; NM_000455.5:c.1226G>A was not mentioned.Does not name this variant
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PMID 25645574 ↗ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.Syngal S et al. · 2015ACG clinical guideline on genetic testing and management of hereditary gastrointestinal cancer syndromes including Peutz-Jeghers syndrome. NM_000455.5:c.1226G>A was not mentioned.Does not name this variant
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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 standards and guidelines for the interpretation of sequence variants. Foundational methodology paper; NM_000455.5:c.1226G>A was not mentioned.Does not name this variant
-
PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Described a standardized DNA variant scoring system for Mendelian disorders using a 7-point scale. Methodology paper; NM_000455.5:c.1226G>A was not mentioned.Does not name this variant
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PMID 34326862 ↗Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach.Bhai P et al. · 2021Analyzed sequence and copy number variants in a Canadian patient cohort with familial cancer syndromes using NGS-based targeted panels. NM_000455.5:c.1226G>A was not identified in the full text of this paper.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 recommendations for cancer genetic risk assessment and counseling. NM_000455.5:c.1226G>A was not mentioned.Does not name this variant
-
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
52 / 1,587,284 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
11 Uncertain significance · 2 Likely benign · 1 Uncertain Significance · 1 Benign
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/142292/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/19-1226570-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr19-1226571-G-A?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/19-1226571-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000455.5%3Ac.1226…
- OncoKB ↗www.oncokb.org/gene/STK11/R409Q
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=127227933
- 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
This variant is present in gnomAD v4.1 (AF= 3.27604e-05; MAF= 0.00328%, 52/1587284 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 4.03964e-05; MAF= 0.00404%, 3/74264 alleles, homozygotes = 0); grpmax FAF= 3.099e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.6169e-05; MAF= 0.00362%, 7/193536 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000198649; MAF= 0.01986%, 1/5034 alleles, homozygotes = 0); grpmax FAF= 2.36e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0001086130118388183, 2/18414 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Uncertain significance (11 clinical laboratories) and as Likely benign (2 clinical laboratories) and as Uncertain Significance (1 clinical laboratory) and as Benign (1 clinical laboratory). (ClinVarID = 142292)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.122. BayesDel score = -0.513561.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. STK11, a tumor suppressor and intracellular kinase, is frequently mutated in lung cancer.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV53071079, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.