rs587782424
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000455.5(STK11):c.402_403del(p.Cys134TrpfsTer28) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. V133V) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 34)
Consequence
STK11
NM_000455.5 frameshift
NM_000455.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.70
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 19-1219345-CGT-C is Pathogenic according to our data. Variant chr19-1219345-CGT-C is described in ClinVar as [Pathogenic]. Clinvar id is 182913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-1219345-CGT-C is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.402_403del | p.Cys134TrpfsTer28 | frameshift_variant | 3/10 | ENST00000326873.12 | |
STK11 | NM_001407255.1 | c.402_403del | p.Cys134TrpfsTer28 | frameshift_variant | 3/9 | ||
STK11 | NR_176325.1 | n.1669_1670del | non_coding_transcript_exon_variant | 4/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.402_403del | p.Cys134TrpfsTer28 | frameshift_variant | 3/10 | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Peutz-Jeghers syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 27, 2023 | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change creates a premature translational stop signal (p.Cys134Trpfs*28) in the STK11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in STK11 are known to be pathogenic (PMID: 15188174, 16287113). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Peutz-Jeghers syndrome (PMID: 20393878). ClinVar contains an entry for this variant (Variation ID: 182913). For these reasons, this variant has been classified as Pathogenic. - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 20, 2014 | The presence of the c.402_403delTG mutation was confirmed in the submitted specimen. The c.402_403delTG mutation in the STK11 gene causes a frameshift starting with codon Cysteine 134, changes this amino acid to a Tryptophan residue, and creates a premature Stop codon at position 28 of the new reading frame, denoted p.Cys134TrpfsX28. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense mediated mRNA decay. Although this mutation has not been previously reported to our knowledge. The variant is found in STK11 panel(s). - |
Computational scores
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at