VCV000182881.39 - ClinVar

NM_000455.5(STK11):c.597+14del

Germline

Classification

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.

(15)

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.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000455.5(STK11):c.597+14del

Variation ID: 182881 Accession: VCV000182881.39

Type and length

Deletion, 1 bp

Location

Cytogenetic: 19p13.3 19: 1220519 (GRCh38) [ NCBI UCSC ] 19: 1220518 (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	Feb 24, 2015	Oct 20, 2024	Jul 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000455.5:c.597+14del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_000455.5:c.597+14delA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000455.4:c.597+14del
NM_000455.4:c.597+14delA
NC_000019.10:g.1220519del
NC_000019.9:g.1220518del
NG_007460.2:g.36113del
LRG_319:g.36113del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000019.10:1220518:A:

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.00080 ()

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00059

The Genome Aggregation Database (gnomAD) 0.00067

Trans-Omics for Precision Medicine (TOPMed) 0.00070

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00078

Exome Aggregation Consortium (ExAC) 0.00079

1000 Genomes Project 0.00080

1000 Genomes Project 30x 0.00156

Links

ClinGen: CA023101 dbSNP: rs536282050 VarSome

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
Gene	OMIM	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.
Hereditary cancer-predisposing syndrome	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Apr 1, 2015	RCV000160973.15
Peutz-Jeghers syndrome	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV000352916.20
not provided	Likely benign (5)	criteria provided, multiple submitters, no conflicts	Jul 1, 2024	RCV000679321.28
Malignant tumor of breast	Likely benign (1)	no assertion criteria provided	-	RCV001356292.10
not specified	Likely benign (1)	criteria provided, single submitter	Aug 15, 2023	RCV002465540.10
Breast and/or ovarian cancer	Likely benign (1)	criteria provided, single submitter	May 31, 2023	RCV003149982.10

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.
Likely benign (Apr 01, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000686666.2 First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022
Likely benign (Jul 25, 2016)	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015)) Method: clinical testing	Peutz-Jeghers syndrome Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000488965.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 24, 2022
Likely benign (May 31, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) 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: SCV003838159.2 First in ClinVar: Mar 11, 2023 Last updated: Feb 04, 2024
Benign (Feb 21, 2014)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	Neoplastic Syndromes, Hereditary Affected status: yes Allele origin: germline	GeneDx Accession: SCV000211682.2 First in ClinVar: Feb 24, 2015 Last updated: Feb 24, 2015	Comment: The variant is found in BR-OV-HEREDIC,COLO-HEREDIC panel(s).
Likely benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Peutz-Jeghers Syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000410739.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Likely benign (Oct 19, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000806083.1 First in ClinVar: Sep 14, 2018 Last updated: Sep 14, 2018
Likely benign (Jul 05, 2021)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV002048364.1 First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022
Likely benign (Jul 15, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Peutz-Jeghers syndrome Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002057419.1 First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022
Likely benign (Aug 15, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV002761024.3 First in ClinVar: Dec 17, 2022 Last updated: Aug 18, 2023
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Peutz-Jeghers syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002366531.3 First in ClinVar: Apr 02, 2022 Last updated: Feb 14, 2024
Likely benign (Nov 06, 2014)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002658361.2 First in ClinVar: Nov 29, 2022 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 (Jul 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV004701684.8 First in ClinVar: Mar 10, 2024 Last updated: Oct 20, 2024	Comment: STK11: BS1 Number of individuals with the variant: 4
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001923292.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
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: SCV001551420.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021	Comment: The STK11 c.597+14delA variant was not identified in the literature nor was it identified in the Cosmic, MutDB, Zhejiang Colon Cancer Database, or Insight Hereditary … (more) The STK11 c.597+14delA variant was not identified in the literature nor was it identified in the Cosmic, MutDB, Zhejiang Colon Cancer Database, or Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs536282050) as â€šÃ„ÃºWith Likely benign allele,â€šÃ„Ã¹ ClinVar (as benign by GeneDx and likely benign by Illumina, Counsyl, and Color Genomics), Clinvitae (2x as in ClinVar), and LOVD 3.0 (2x as likely benign) databases. The variant was identified in control databases in 1 of 30810 chromosomes at a frequency of 0.000032 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 1 of 8678 chromosomes (freq: 0.000115), while the variant was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), European (Non-Finnish), Latino, Other, and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The variant was identified with a co-occurring pathogenic NBN variant (p.Lys233SerfsX5), increasing the likelihood that the c.597+14delA variant does not have clinical significance. 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)
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, Amsterdam University Medical Center Study: VKGL Data-share Consensus Accession: SCV001807663.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021
click to load more click to collapse

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 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.

Comment:

The STK11 c.597+14delA variant was not identified in the literature nor was it identified in the Cosmic, MutDB, Zhejiang Colon Cancer Database, or Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs536282050) as â€šÃ„ÃºWith Likely benign allele,â€šÃ„Ã¹ ClinVar (as benign by GeneDx and likely benign by Illumina, Counsyl, and Color Genomics), Clinvitae (2x as in ClinVar), and LOVD 3.0 (2x as likely benign) databases. The variant was identified in control databases in 1 of 30810 chromosomes at a frequency of 0.000032 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 1 of 8678 chromosomes (freq: 0.000115), while the variant was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), European (Non-Finnish), Latino, Other, and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The variant was identified with a co-occurring pathogenic NBN variant (p.Lys233SerfsX5), increasing the likelihood that the c.597+14delA variant does not have clinical significance. 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.

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.

Comment:

Citations for germline classification of this variant

There 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 rs536282050 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_000455.5(STK11):c.597+14del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs536282050 ...