VCV000833462.1 - ClinVar

NC_000019.9:g.(?_852319)_(1226656_?)del

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.

(1)

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.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000019.9:g.(?_852319)_(1226656_?)del

Variation ID: 833462 Accession: VCV000833462.1

Type and length

Deletion, 374,338 bp

Location

Cytogenetic: 19p13.3 19: 852319-1226656 (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	Apr 15, 2020	Apr 15, 2020	Apr 1, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NC_000019.9:g.(?_852319)_(1226656_?)del

Protein change

Other names

Canonical SPDI

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.

Links

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	2398	2676
ELANE		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	556	600
GRIN3B		Dosage sensitivity unlikely	No evidence available	GRCh38 GRCh37	135	176
ABCA7		-	-	GRCh38 GRCh37	312	358
ARHGAP45		-	-	GRCh38 GRCh37	24	68
ARID3A		-	-	GRCh38 GRCh37	52	93
CFD		-	-	GRCh38 GRCh38 GRCh37	248	292
CNN2		-	-	GRCh38 GRCh37	21	61
GPX4		-	-	GRCh38 GRCh37	136	203
KISS1R		-	-	GRCh38 GRCh37	132	178

There are 6 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh37) and ClinGen Dosage Sensitivity Map.

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.
Peutz-Jeghers syndrome	Pathogenic (1)	criteria provided, single submitter	Apr 1, 2019	RCV001033903.2

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.
Pathogenic (Apr 01, 2019)	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: SCV001197210.1 First in ClinVar: Apr 15, 2020 Last updated: Apr 15, 2020	Publications: PubMed (6) PubMed: 16648371‚ 16287113‚ 17924967‚ 22382802‚ 23399955‚ 20623358 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the STK11 gene has been identified. The boundaries of this event are … (more) A gross deletion of the genomic region encompassing the full coding sequence of the STK11 gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. Large deletions involving the STK11 gene account for about 30% of the Peutz Jeghers syndrome (PJS) cases (PMID: 20623358). Whole gene deletions of STK11 have been reported in several individuals affected with PJS (PMID: 23399955, 17924967, 16287113, 22382802, 16648371, Invitae) Loss-of-function variants in STK11 are known to be pathogenic (PMID: 15188174, 16287113). For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the STK11 gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. Large deletions involving the STK11 gene account for about 30% of the Peutz Jeghers syndrome (PJS) cases (PMID: 20623358). Whole gene deletions of STK11 have been reported in several individuals affected with PJS (PMID: 23399955, 17924967, 16287113, 22382802, 16648371, Invitae) Loss-of-function variants in STK11 are known to be pathogenic (PMID: 15188174, 16287113). For these reasons, this variant has been classified as Pathogenic.

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

Title	Author	Journal	Year	Link
Prevalence of germline PTEN, BMPR1A, SMAD4, STK11, and ENG mutations in patients with moderate-load colorectal polyps.	Ngeow J	Gastroenterology	2013	PMID: 23399955
Exon-level array CGH in a large clinical cohort demonstrates increased sensitivity of diagnostic testing for Mendelian disorders.	Aradhya S	Genetics in medicine : official journal of the American College of Medical Genetics	2012	PMID: 22382802
Breakpoint determination of 15 large deletions in Peutz-Jeghers subjects.	Resta N	Human genetics	2010	PMID: 20623358
Genetic defects underlying Peutz-Jeghers syndrome (PJS) and exclusion of the polarity-associated MARK/Par1 gene family as potential PJS candidates.	de Leng WW	Clinical genetics	2007	PMID: 17924967
LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers syndrome.	Volikos E	Journal of medical genetics	2006	PMID: 16648371
High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome.	Aretz S	Human mutation	2005	PMID: 16287113

Text-mined citations for this variant ...

Record last updated Oct 08, 2024

ClinVar Genomic variation as it relates to human health

NC_000019.9:g.(?_852319)_(1226656_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...