ClinVar Genomic variation as it relates to human health
NM_000455.5(STK11):c.734+1G>A
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000455.5(STK11):c.734+1G>A
Variation ID: 1068630 Accession: VCV001068630.12
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.3 19: 1220718 (GRCh38) [ NCBI UCSC ] 19: 1220717 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline May 10, 2021 May 1, 2024 Dec 26, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000455.5:c.734+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001407255.1:c.734+1G>A splice donor NC_000019.10:g.1220718G>A NC_000019.9:g.1220717G>A NG_007460.2:g.36312G>A LRG_319:g.36312G>A LRG_319t1:c.734+1G>A - Protein change
- Other names
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- Canonical SPDI
- NC_000019.10:1220717:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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STK11 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2394 | 2672 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Dec 26, 2023 | RCV001380249.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 3, 2021 | RCV002384545.2 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jun 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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Peutz-Jeghers syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001748833.1
First in ClinVar: Jul 10, 2021 Last updated: Jul 10, 2021 |
Comment:
Variant summary: STK11 c.734+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to … (more)
Variant summary: STK11 c.734+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5 splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 239620 control chromosomes (gnomAD). c.734+1G>A has been reported in the literature in individuals affected with Peutz-Jeghers Syndrome (e.g. Olschwang_2001, Lim_2003, Wang_2014, Zhang_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jul 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Peutz-Jeghers syndrome
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002057377.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
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Pathogenic
(Dec 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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Peutz-Jeghers syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001578244.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects a donor splice site in intron 5 of the STK11 gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects a donor splice site in intron 5 of the STK11 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in STK11 are known to be pathogenic (PMID: 15188174, 16287113). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Peutz-Jeghers syndrome (PMID: 11389158, 24652667). This variant is also known as IVS5+1g>a. ClinVar contains an entry for this variant (Variation ID: 1068630). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Dec 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002674953.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.734+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 5 of the STK11 gene. This variant has … (more)
The c.734+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 5 of the STK11 gene. This variant has been detected in multiple individuals and/or families diagnosed with Peutz-Jeghers Syndrome (Olschwang S et al. J Med Genet, 2001 Jun;38:356-60; Lim W et al. Br J Cancer, 2003 Jul;89:308-13; Wang Z et al. Hum Mutat, 2014 Jul;35:851-8; Ambry internal data). Of note, this variant is also designated as IVS5+1G>A in some literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and may result in the creation or strengthening of a novel splice donor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Mutation analysis of related genes in hamartoma polyp tissue of Peutz-Jeghers syndrome. | Zhang Z | World journal of gastroenterology | 2020 | PMID: 32390703 |
STK11 domain XI mutations: candidate genetic drivers leading to the development of dysplastic polyps in Peutz-Jeghers syndrome. | Wang Z | Human mutation | 2014 | PMID: 24652667 |
High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome. | Aretz S | Human mutation | 2005 | PMID: 16287113 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Relative frequency and morphology of cancers in STK11 mutation carriers. | Lim W | Gastroenterology | 2004 | PMID: 15188174 |
Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome. | Lim W | British journal of cancer | 2003 | PMID: 12865922 |
Peutz-Jeghers families unlinked to STK11/LKB1 gene mutations are highly predisposed to primitive biliary adenocarcinoma. | Olschwang S | Journal of medical genetics | 2001 | PMID: 11389158 |
Text-mined citations for rs587782018 ...
HelpRecord last updated Oct 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.