19-1221203-CGAAAT-C
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_000455.5(STK11):c.735-6_735-2del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,611,456 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
STK11
NM_000455.5 splice_region, splice_polypyrimidine_tract, intron
NM_000455.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.697
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_benign. Variant got -5 ACMG points.
BP6
Variant 19-1221203-CGAAAT-C is Benign according to our data. Variant chr19-1221203-CGAAAT-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 371789.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=5, Uncertain_significance=2, Benign=1}.
BS2
High AC in GnomAdExome4 at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.735-6_735-2del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000326873.12 | |||
STK11 | NM_001407255.1 | c.735-6_735-2del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
STK11 | NR_176325.1 | n.2002-6_2002-2del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.735-6_735-2del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152180Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000444 AC: 11AN: 247506Hom.: 0 AF XY: 0.0000519 AC XY: 7AN XY: 134800
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GnomAD4 exome AF: 0.0000110 AC: 16AN: 1459158Hom.: 0 AF XY: 0.0000152 AC XY: 11AN XY: 725696
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152298Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74462
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:6
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Peutz-Jeghers syndrome Uncertain:2Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Apr 12, 2023 | This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Nov 18, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jul 12, 2016 | - - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Nov 27, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 20, 2022 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at