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STK11
Final classification
VUS
STK11 c.*16+7C>T · p.?
STK11

The STK11 c.*16+7C>T (p.?) variant has been reported in ClinVar as likely benign by two clinical laboratories, and no expert-panel review was identified.

Gene
STK11
Transcript
NM_000455.5
HGVS · transcript:coding
NM_000455.5:c.*16+7C>T
Consequence
N/A
GRCh38
chr19:1226670 C>T
GRCh37
chr19:1226669 C>T
Basis 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 because the evidence is conflicting. ▾
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 because the evidence is conflicting.
Classification rationale
PM2 BP4 VUS
STK11 c.*16+7C>T

The STK11 c.*16+7C>T (p.?) variant has been reported in ClinVar as likely benign by two clinical laboratories, and no expert-panel review was identified.1 This variant is present at low frequency in gnomAD, with AF 0.00639% in v2.1 and AF 0.00677% in v4.1; these values remain below the 0.1% PM2 threshold.2 In silico splice prediction does not support a damaging effect, with SpliceAI showing a maximum delta score of 0.01, consistent with no significant splice impact.3

PM2 + BP4 → VUS
1 clinvar ↗
2 gnomad_v2 ↗gnomad_v4 ↗
3 spliceai ↗
Gene diagram · NM_000455.5 · variants mapped to exon structure
STK11 NM_000455.5
Fetching transcript structure from UCSC…
Applied criteria · 2 met · select any tile
Met
Not met
Not assessed
N/A
Strength very strong supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
—
—
—
Rationale
Select a criterion.
Sources
Evidence used
    Gaps remaining
      Rule
      —
      Research & evidence
      Population frequency
      gnomAD v4.1 screenshot
      gnomAD v4.1
      gnomAD v2.1 screenshot
      gnomAD v2.1
      v4.1
      This variant is present in gnomAD v4.1 (AF= 6.77486e-05; MAF= 0.00677%, 101/1490806 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.26896e-05; MAF= 0.00827%, 93/1124688 alleles, homozygotes = 0); grpmax FAF= 6.881e-05.
      v2.1
      This variant is present in gnomAD v2.1 (AF= 6.39376e-05; MAF= 0.00639%, 8/125122 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000145709; MAF= 0.01457%, 2/13726 alleles, homozygotes = 0); grpmax FAF= 5.434e-05.
      Allele frequency by ancestry
      three datasets · side by side
      gnomAD v4.1
      0.0068% · 101 / 1,490,806
      0 hom · FAF 0.0069%
      European (non-Finnish)
      93 / 1,124,688
      0.0083%
      East Asian
      3 / 39,896
      0.0075%
      African/African American
      3 / 70,684
      0.0042%
      Remaining individuals
      1 / 57,670
      0.0017%
      South Asian
      1 / 76,142
      0.0013%
      + 5 not observed (Admixed American, European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish)
      gnomAD v2.1
      0.0064% · 8 / 125,122
      0 hom · FAF 0.0054%
      African/African American
      2 / 13,726
      0.015%
      European (non-Finnish)
      6 / 51,282
      0.012%
      + 6 not observed (Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian)
      gnomAD v4 ↗ gnomAD v2 ↗
      ClinVar screenshot
      ClinVar
      This variant has been reported in ClinVar as Likely benign (2 clinical laboratories).
      ClinVar ↗
      SpliceAI screenshot
      In silico
      SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
      SpliceAI ↗
      Functional No data
      No calibrated functional assay or RNA evidence was identified for this variant.
      OncoKB ↗
      COSMIC screenshot
      COSMIC
      Somatic evidence
      COSMIC
      This variant has not previously been reported in somatic cancers (COSMIC).
      Hotspots
      This variant does not lie in a statistically significant cancer hotspot.
      COSMIC ↗
      Sources & reference links
      6Sources
      ClinVar
      gnomAD v2.1
      gnomAD v4.1
      SpliceAI
      OncoKB
      COSMIC