19-1221294-C-T
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_000455.5(STK11):c.816C>T(p.Tyr272=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00467 in 1,611,214 control chromosomes in the GnomAD database, including 280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.024 ( 128 hom., cov: 33)
Exomes 𝑓: 0.0027 ( 152 hom. )
Consequence
STK11
NM_000455.5 synonymous
NM_000455.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.07
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 Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 19-1221294-C-T is Benign according to our data. Variant chr19-1221294-C-T is described in ClinVar as [Benign]. Clinvar id is 141192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-1221294-C-T is described in Lovd as [Benign]. Variant chr19-1221294-C-T is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.079 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.816C>T | p.Tyr272= | synonymous_variant | 6/10 | ENST00000326873.12 | |
STK11 | NM_001407255.1 | c.816C>T | p.Tyr272= | synonymous_variant | 6/9 | ||
STK11 | NR_176325.1 | n.2083C>T | non_coding_transcript_exon_variant | 7/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.816C>T | p.Tyr272= | synonymous_variant | 6/10 | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0239 AC: 3630AN: 152194Hom.: 129 Cov.: 33
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GnomAD3 exomes AF: 0.00581 AC: 1422AN: 244572Hom.: 52 AF XY: 0.00432 AC XY: 576AN XY: 133204
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GnomAD4 exome AF: 0.00267 AC: 3889AN: 1458902Hom.: 152 Cov.: 31 AF XY: 0.00230 AC XY: 1670AN XY: 725584
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GnomAD4 genome AF: 0.0239 AC: 3638AN: 152312Hom.: 128 Cov.: 33 AF XY: 0.0231 AC XY: 1719AN XY: 74474
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ClinVar
Significance: Benign
Submissions summary: Benign:18
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:7
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jul 05, 2018 | - - |
Benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Peutz-Jeghers syndrome Benign:4
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Hereditary cancer-predisposing syndrome Benign:3
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 20, 2015 | - - |
Likely benign, no assertion criteria provided | clinical testing | True Health Diagnostics | Feb 20, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 18, 2014 | 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:2
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Breast and/or ovarian cancer Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Oct 05, 2021 | - - |
Malignant tumor of breast Benign:1
Benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The STK11 p.Tyr272Tyr variant was not identified in the literature nor was it identified in the MutDB, LOVD 3.0, Zhejiang Colon Cancer Database, and Insight Hereditary Tumors Database databases. The variant was identified in dbSNP (ID: rs9282859) as “Other”, ClinVar (classified benign by Ambry Genetics and Prevention Genetics, and likely benign by Illumina), and in Cosmic (3X all in lung carcinomas). The variant was also identified in control databases in 2204 (84 homozygous) of 273338 chromosomes at a frequency of 0.008 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017), identified in the following populations at a frequency greater than 1%: African in 1993 of 23530 chromosomes (freq: 0.085). The p.Tyr272Tyr variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at