rs1555738874
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000455.5(STK11):c.895_901dup(p.Arg301LeufsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). 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: -0.228
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 12 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 19-1221979-T-TCTCCATC is Pathogenic according to our data. Variant chr19-1221979-T-TCTCCATC is described in ClinVar as [Pathogenic]. Clinvar id is 527814.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.895_901dup | p.Arg301LeufsTer19 | frameshift_variant | 7/10 | ENST00000326873.12 | |
STK11 | NM_001407255.1 | c.895_901dup | p.Arg301LeufsTer19 | frameshift_variant | 7/9 | ||
STK11 | NR_176325.1 | n.2162_2168dup | non_coding_transcript_exon_variant | 8/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.895_901dup | p.Arg301LeufsTer19 | frameshift_variant | 7/10 | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Peutz-Jeghers syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 05, 2018 | This sequence change creates a premature translational stop signal (p.Arg301Leufs*19) in the STK11 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with STK11-related disease. Loss-of-function variants in STK11 are known to be pathogenic (PMID: 15188174, 16287113). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at