VCV000182885.52 - ClinVar

NM_000455.5(STK11):c.795G>A (p.Glu265=)

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.

(17)

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.795G>A (p.Glu265=)

Variation ID: 182885 Accession: VCV000182885.52

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19p13.3 19: 1221273 (GRCh38) [ NCBI UCSC ] 19: 1221272 (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	Jun 1, 2016	Oct 20, 2024	Jan 31, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000455.5:c.795G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000446.1:p.Glu265=	synonymous
NC_000019.10:g.1221273G>A
NC_000019.9:g.1221272G>A
NG_007460.2:g.36867G>A
LRG_319:g.36867G>A
LRG_319t1:c.795G>A	LRG_319p1:p.Glu265=

... more HGVS ... less HGVS

Protein change

Other names

p.E265E:GAG>GAA

Canonical SPDI

NC_000019.10:1221272:G: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.

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

The Genome Aggregation Database (gnomAD) 0.00004

Trans-Omics for Precision Medicine (TOPMed) 0.00008

Exome Aggregation Consortium (ExAC) 0.00019

Links

ClinGen: CA023279 dbSNP: rs730881963 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	Jul 29, 2021	RCV000160977.10
Peutz-Jeghers syndrome	Benign/Likely benign (7)	criteria provided, multiple submitters, no conflicts	Jan 31, 2024	RCV000204976.21
not specified	Benign (2)	criteria provided, multiple submitters, no conflicts	Jan 1, 2022	RCV000213019.2
not provided	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Apr 18, 2023	RCV000679324.27
Familial ovarian cancer	Benign (1)	no assertion criteria provided	-	RCV001358138.2
Breast and/or ovarian cancer	Likely benign (1)	criteria provided, single submitter	Sep 26, 2022	RCV003492659.1

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 (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: SCV002057282.1 First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022
Benign (Jan 01, 2022)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002074229.1 First in ClinVar: Feb 12, 2022 Last updated: Feb 12, 2022
Likely benign (Jun 01, 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: SCV000488732.2 First in ClinVar: Jul 01, 2016 Last updated: Dec 24, 2022
Benign (Jul 07, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Peutz-Jeghers syndrome Affected status: yes Allele origin: germline	KCCC/NGS Laboratory, Kuwait Cancer Control Center Accession: SCV004015575.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023
Benign (Apr 18, 2023)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV001134849.3 First in ClinVar: Jan 04, 2020 Last updated: Jan 06, 2024
Likely benign (Sep 26, 2022)	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: SCV004239731.1 First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024
Likely Benign (Jan 11, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) 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: SCV004818909.1 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: 18
Likely benign (Jul 17, 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: SCV000212950.7 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)
Benign (Jul 11, 2014)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000211687.10 First in ClinVar: Feb 24, 2015 Last updated: Jun 01, 2016	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Likely benign (Oct 24, 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: SCV000806086.1 First in ClinVar: Sep 14, 2018 Last updated: Sep 14, 2018
Likely benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Peutz-Jeghers syndrome Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001140939.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Benign (Jul 29, 2021)	criteria provided, single submitter (Sema4 Curation Guidelines) Method: curation	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Sema4, Sema4 Accession: SCV002526938.1 First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Likely benign (Mar 06, 2016)	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: SCV000686690.2 First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022
Benign (Apr 13, 2023)	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023)) Method: clinical testing	Peutz-Jeghers syndrome Affected status: unknown Allele origin: unknown	Myriad Genetics, Inc. Accession: SCV004017962.1 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.
Benign (Jan 31, 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: SCV000260114.11 First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024
Likely benign (Nov 01, 2022)	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: SCV001151579.21 First in ClinVar: Feb 03, 2020 Last updated: Oct 20, 2024	Comment: STK11: BP4, BP7 Number of individuals with the variant: 1
Benign (-)	no assertion criteria provided Method: clinical testing	Familial ovarian cancer 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: SCV001553798.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021	Comment: The STK11 p.Glu265= variant was not identified in the literature nor was it identified in the Cosmic, MutDB, LOVD 3.0, Zhejiang Colon Cancer Database, and … (more) The STK11 p.Glu265= variant was not identified in the literature nor was it identified in the Cosmic, MutDB, LOVD 3.0, Zhejiang Colon Cancer Database, and Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs730881963) â€šÃ„ÃºWith Likely benign alleleâ€šÃ„Ã¹, ClinVar (classified as benign by GeneDx and likely benign by Ambry Genetics, Invitae and Counsyl), Clinvitae (3x), and in control databases in 50 (1 homozygous) of 275192 chromosomes at a frequency of 0.0002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). Breakdown of the observations by population include, other in 4 of 6416 chromosomes (freq. 0.0006), Latino in 18 (1 homozygous) of 34300 chromosomes (freq. 0.0005), European Non-Finnish in 5 of 125550 chromosomes (freq. 0.00004), and South Asian in 23 of 30524 chromosomes (freq. 0.0007); it was not seen in the African, Ashkenazi Jewish, European Finnish, and East Asian populations. The variant was identified by our laboratory in 1 individual with breast cancer, co-occurring with a pathogenic BRCA2 variant (c.6359C>G/ p.Ser2120X), increasing the likelihood that the p.Glu265=variant does not have clinical significance.The p.Glu265= 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 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. (less) Number of individuals with the variant: 1
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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:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

The STK11 p.Glu265= variant was not identified in the literature nor was it identified in the Cosmic, MutDB, LOVD 3.0, Zhejiang Colon Cancer Database, and Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs730881963) â€šÃ„ÃºWith Likely benign alleleâ€šÃ„Ã¹, ClinVar (classified as benign by GeneDx and likely benign by Ambry Genetics, Invitae and Counsyl), Clinvitae (3x), and in control databases in 50 (1 homozygous) of 275192 chromosomes at a frequency of 0.0002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). Breakdown of the observations by population include, other in 4 of 6416 chromosomes (freq. 0.0006), Latino in 18 (1 homozygous) of 34300 chromosomes (freq. 0.0005), European Non-Finnish in 5 of 125550 chromosomes (freq. 0.00004), and South Asian in 23 of 30524 chromosomes (freq. 0.0007); it was not seen in the African, Ashkenazi Jewish, European Finnish, and East Asian populations. The variant was identified by our laboratory in 1 individual with breast cancer, co-occurring with a pathogenic BRCA2 variant (c.6359C>G/ p.Ser2120X), increasing the likelihood that the p.Glu265=variant does not have clinical significance.The p.Glu265= 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 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as 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 rs730881963 ...

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 Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_000455.5(STK11):c.795G>A (p.Glu265=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs730881963 ...