rs1131690935
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM4PP5_Moderate
The NM_000455.5(STK11):c.890_907del(p.Arg297_Gln302del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 34)
Consequence
STK11
NM_000455.5 inframe_deletion
NM_000455.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.73
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 Likely_pathogenic. Variant got 8 ACMG points.
PM1
?
In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 14 uncertain in NM_000455.5
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_000455.5.
PP5
?
Variant 19-1221972-AAGAGGTTCTCCATCCGGC-A is Pathogenic according to our data. Variant chr19-1221972-AAGAGGTTCTCCATCCGGC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 428771.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.890_907del | p.Arg297_Gln302del | inframe_deletion | 7/10 | ENST00000326873.12 | |
STK11 | NM_001407255.1 | c.890_907del | p.Arg297_Gln302del | inframe_deletion | 7/9 | ||
STK11 | NR_176325.1 | n.2157_2174del | non_coding_transcript_exon_variant | 8/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.890_907del | p.Arg297_Gln302del | inframe_deletion | 7/10 | 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: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 19, 2016 | The c.890_907del18 variant (also known as p.R297_Q302del) is located in coding exon 7 of the STK11 gene. This variant results from an in-frame deletion of 18 nucleotides (GGTTCTCCATCCGGCAGA) between nucleotide positions 890 and 907. This results in the deletion of 6 amino acid residues between codons 297 and 302. This alteration has been identified in an individual with a clinical diagnosis of Peutz-Jeghers syndrome (Ambry internal data). Other alterations occurring in this region have been shown to be pathogenic (Wang Z, Hum. Mutat. 2014 Jul; 35(7):851-8; Westerman AM, Hum. Mutat. 1999 ; 13(6):476-81), however this specific variant has not been reported in the literature to date. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6026 samples (12052 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 125000 alleles tested) in our clinical cohort. The deleted amino acid positions are well conserved in available vertebrate species. In addition, this deletion is predicted to be highly deleterious by the PROVEAN in silico analysis tool (Choi Y, PLoS ONE 2012 ; 7(10):e46688). Based on the majority of available evidence to date, this variant is likely to be pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at