19-1207022-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000455.5(STK11):c.109C>T(p.Gln37Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
STK11
NM_000455.5 stop_gained
NM_000455.5 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 5.68
Genes affected
STK11 (HGNC:11389): (serine/threonine kinase 11) The protein encoded by this gene is a serine/threonine kinase that regulates cell polarity and energy metabolism and functions as a tumor suppressor. Mutations in this gene have been associated with the autosomal dominant Peutz-Jeghers syndrome, as well as with skin, pancreatic, and testicular cancers. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-1207022-C-T is Pathogenic according to our data. Variant chr19-1207022-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 376334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.109C>T | p.Gln37Ter | stop_gained | 1/10 | ENST00000326873.12 | |
STK11 | NM_001407255.1 | c.109C>T | p.Gln37Ter | stop_gained | 1/9 | ||
STK11 | NR_176325.1 | n.1245C>T | non_coding_transcript_exon_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.109C>T | p.Gln37Ter | stop_gained | 1/10 | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Peutz-Jeghers syndrome Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 13, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in STK11 are known to be pathogenic. This particular variant has been reported in the literature in at least one individual with Peutz-Jeghers syndrome (PMID: 15188174). This sequence change creates a premature translational stop signal at codon 37 (p.Gln37*) of the STK11 gene. It is expected to result in an absent or disrupted protein product. - |
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Feb 09, 2024 | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. - |
Neoplasm Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | Jul 14, 2015 | - - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 26, 2021 | The p.Q37* pathogenic mutation (also known as c.109C>T), located in coding exon 1 of the STK11 gene, results from a C to T substitution at nucleotide position 109. This changes the amino acid from a glutamine to a stop codon within coding exon 1. This mutation has been reported in multiple individuals fulfilling criteria for a clinical diagnosis of Peutz-Jeghers syndrome (PJS) (Lim W et al. Gastroenterology. 2004 Jun;126(7):1788-94; Hearle N et al. Clin Cancer Res. 2006 May 15;12(10):3209-15; Jiang YL et al. Cancer Genet, 2019 01;230:47-57). In addition, in vivo functional studies demonstrate that this alteration confers tumorigenicity (Dahmani R et al. Oncogene, 2015 Apr;34:2337-46). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at