19-1207065-TGGG-TGGGG
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000455.5(STK11):c.157dup(p.Asp53GlyfsTer110) 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 (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
STK11
NM_000455.5 frameshift
NM_000455.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.65
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 19-1207065-T-TG is Pathogenic according to our data. Variant chr19-1207065-T-TG is described in ClinVar as [Pathogenic]. Clinvar id is 527822.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.157dup | p.Asp53GlyfsTer110 | frameshift_variant | 1/10 | ENST00000326873.12 | |
STK11 | NM_001407255.1 | c.157dup | p.Asp53GlyfsTer110 | frameshift_variant | 1/9 | ||
STK11 | NR_176325.1 | n.1293dup | non_coding_transcript_exon_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.157dup | p.Asp53GlyfsTer110 | frameshift_variant | 1/10 | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 16, 2022 | The c.157dupG pathogenic mutation, located in coding exon 1 of the STK11 gene, results from a duplication of G at nucleotide position 157, causing a translational frameshift with a predicted alternate stop codon (p.D53Gfs*110). This alteration has been detected in multiple individuals with Peutz-Jeghers syndrome (PJS), and was shown to segregate with disease in at least one family (Trojan J et al. Am J Gastroenterol, 1999 Jan;94:257-61; Aretz S et al. Hum Mutat, 2005 Dec;26:513-9; Borun P et al. BMC Med Genet, 2013 May;14:58). 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. - |
Peutz-Jeghers syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2019 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in STK11 are known to be pathogenic (PMID: 15188174, 16287113). This variant has been reported in individuals affected with Peutz-Jeghers syndrome (PJS) and to segregate with the disease in at least one family (PMID: 16287113, 9934767, 23718779). ClinVar contains an entry for this variant (Variation ID: 527822). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asp53Glyfs*110) in the STK11 gene. It is expected to result in an absent or disrupted protein product. - |
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