ClinVar Genomic variation as it relates to human health
NM_000455.5(STK11):c.666C>T (p.Pro222=)
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
-
NM_000455.5(STK11):c.666C>T (p.Pro222=)
Variation ID: 183713 Accession: VCV000183713.40
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 19p13.3 19: 1220649 (GRCh38) [ NCBI UCSC ] 19: 1220648 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Dec 6, 2016 Oct 8, 2024 Jan 31, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000455.5:c.666C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000446.1:p.Pro222= synonymous NC_000019.10:g.1220649C>T NC_000019.9:g.1220648C>T NG_007460.2:g.36243C>T LRG_319:g.36243C>T LRG_319t1:c.666C>T LRG_319p1:p.Pro222= - Protein change
- Other names
- -
- Canonical SPDI
- NC_000019.10:1220648:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
0.00060 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00047
1000 Genomes Project 0.00060
Exome Aggregation Consortium (ExAC) 0.00082
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD) 0.00005
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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. |
|||
STK11 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2394 | 2672 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Apr 28, 2021 | RCV000162395.8 | |
Benign/Likely benign (7) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2024 | RCV000228328.23 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Oct 23, 2019 | RCV000423666.5 | |
Likely benign (1) |
no assertion criteria provided
|
- | RCV001356479.3 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Oct 1, 2023 | RCV001704153.11 | |
Likely benign (1) |
criteria provided, single submitter
|
Jun 5, 2023 | RCV003149986.3 |
Submissions - Germline
Classification
Help
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
Help
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
Help
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
Help
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. |
|
---|---|---|---|---|---|
Benign
(Aug 11, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000686673.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
|
|
Likely benign
(Jun 05, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV003838166.2
First in ClinVar: Mar 11, 2023 Last updated: Feb 04, 2024 |
|
|
Benign
(Apr 23, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000920280.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: STK11 c.666C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these … (more)
Variant summary: STK11 c.666C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00054 in 268862 control chromosomes, predominantly at a frequency of 0.0043 within the South Asian subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 688 fold of the estimated maximal expected allele frequency for a pathogenic variant in STK11 causing Peutz-Jeghers Syndrome phenotype (6.3e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.666C>T in individuals affected with Peutz-Jeghers Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. (less)
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Peutz-Jeghers syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000410741.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
Benign
(Oct 23, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001469920.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
|
|
Likely benign
(Mar 12, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000514796.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely benign
(Jul 15, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Peutz-Jeghers syndrome
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002057423.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
|
|
Benign
(Apr 13, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Peutz-Jeghers syndrome
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV004017961.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
|
|
Likely benign
(Oct 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004139039.9
First in ClinVar: Nov 20, 2023 Last updated: Oct 08, 2024 |
Comment:
STK11: BP4, BP7, BS1
Number of individuals with the variant: 1
|
|
Benign
(Apr 28, 2021)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002531722.1
First in ClinVar: Mar 25, 2020 Last updated: Mar 25, 2020 |
|
|
Likely benign
(Dec 23, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Peutz-Jeghers syndrome
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000488076.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 24, 2022 |
|
|
Benign
(Jul 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Peutz-Jeghers syndrome
Affected status: yes
Allele origin:
germline
|
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004015566.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
|
|
Benign
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Peutz-Jeghers syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000284873.10
First in ClinVar: Jul 01, 2016 Last updated: Feb 14, 2024 |
|
|
Benign
(Jan 11, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Peutz-Jeghers syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004818883.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Number of individuals with the variant: 20
|
|
Likely benign
(Dec 09, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000212718.8
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely 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. (less)
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001551660.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The STK11 p.Pro222= variant was not identified in the literature nor was it identified in Cosmic, MutDB, Zhejiang University Database or Insight Hereditary Tumors Database. … (more)
The STK11 p.Pro222= variant was not identified in the literature nor was it identified in Cosmic, MutDB, Zhejiang University Database or Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs542189325 as “With Likely benign, other allele”), ClinVar (classified benign by Invitae and Color Genomics Inc and as likely benign by Ambry Genetics, Illumina, Counsyl and GeneDx), and LOVD 3.0 (1x). The variant was identified in control databases in 145 of 268862 chromosomes (1 homozygous) at a frequency of 0.0005, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 132 of 30482 chromosomes (freq: 0.004, 1 homozygous), African in 1 of 22816 chromosomes (freq: 0.00004), Latino in 3 of 34078 chromosomes (freq: 0.00009), European Non-Finnish in 6 of 121580 chromosomes (freq: 0.00005), and East Asian in 3 of 18654 chromosomes (freq: 0.0002), while it not observed in the Other, Ashkenazi Jewish or Finnish populations. The p.Pro222= 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. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (less)
|
|
click to load more click to collapse |
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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs542189325 ...
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.