VCV000831623.2 - ClinVar

NC_000010.11:g.(?_86755016)_(87965564_?)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.

(2)

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_000010.11:g.(?_86755016)_(87965564_?)del

Variation ID: 831623 Accession: VCV000831623.2

Type and length

Deletion, 1,210,549 bp

Location

Cytogenetic: 10q23.2-23.31 10: 88514773-89725321 (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	May 10, 2021	Dec 14, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NC_000010.10:g.(?_88514773)_(89725321_?)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.
BMPR1A		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2329	2425
PTEN		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	3098	3607
ADIRF	-	-	-	GRCh38 GRCh37	-	54
ADIRF-AS1	-	-	-	GRCh38 GRCh37	-	54
AGAP11	-	-	-	GRCh38 GRCh37	2	51
ATAD1		-	-	GRCh38 GRCh38 GRCh37	183	213
FAM25A	-	-	-	GRCh38 GRCh37	8	55
GLUD1		-	-	GRCh38 GRCh37	181	287
KLLN		-	-	GRCh38 GRCh38 GRCh37	21	365
MINPP1		-	-	GRCh38 GRCh37	38	85

There are 5 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.
Generalized juvenile polyposis/juvenile polyposis coli	Pathogenic (1)	criteria provided, single submitter	Dec 14, 2019	RCV001032166.2
PTEN hamartoma tumor syndrome	Pathogenic (1)	criteria provided, single submitter	Dec 11, 2019	RCV001380352.2

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 (Dec 14, 2019)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Juvenile polyposis syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001195473.1 First in ClinVar: Apr 15, 2020 Last updated: Apr 15, 2020	Publications: PubMed (5) PubMed: 22993021‚ 16685657‚ 23399955‚ 23331837‚ 18510548 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the BMPR1A 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 BMPR1A 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. A similar deletion of the full coding sequence of BMPR1A has been reported in an individual affected with juvenile polyposis (PMID: 23399955), and larger copy number events that include this gene have been reported (PMID: 18510548, 23331837, 16685657, 22993021). Loss-of-function variants in BMPR1A are known to be pathogenic (PMID: 11536076, 12417513). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Dec 11, 2019)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	PTEN hamartoma tumor syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001578360.1 First in ClinVar: May 10, 2021 Last updated: May 10, 2021	Publications: PubMed (8) PubMed: 23335809‚ 18456716‚ 9286463‚ 16685657‚ 16287957‚ 18510548‚ 9467011‚ 21194675 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the PTEN 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 PTEN 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. A similar whole gene deletion of PTEN has been observed in several individuals affected with Cowden syndrome and clinical features of Bannayan-Riley-Ruvalcaba syndrome (BRRS) (PMID: 23335809, 18456716, 9286463). Additionally, larger deletions within chromosome 10q have also been reported (PMID: 16685657, 16287957, 18510548). Loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). 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 BMPR1A 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. A similar deletion of the full coding sequence of BMPR1A has been reported in an individual affected with juvenile polyposis (PMID: 23399955), and larger copy number events that include this gene have been reported (PMID: 18510548, 23331837, 16685657, 22993021). Loss-of-function variants in BMPR1A are known to be pathogenic (PMID: 11536076, 12417513). For these reasons, this variant has been classified as Pathogenic.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the PTEN 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. A similar whole gene deletion of PTEN has been observed in several individuals affected with Cowden syndrome and clinical features of Bannayan-Riley-Ruvalcaba syndrome (BRRS) (PMID: 23335809, 18456716, 9286463). Additionally, larger deletions within chromosome 10q have also been reported (PMID: 16685657, 16287957, 18510548). Loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). 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
High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome.	Bubien V	Journal of medical genetics	2013	PMID: 23335809
Juvenile polyposis of infancy in a child with deletion of BMPR1A and PTEN genes: surgical approach.	Oliveira PH	Journal of pediatric surgery	2013	PMID: 23331837
A new case with 10q23 interstitial deletion encompassing both PTEN and BMPR1A narrows the genetic region deleted in juvenile polyposis syndrome.	Hiljadnikova Bajro M	Journal of applied genetics	2013	PMID: 22993021
A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands.	Tan MH	American journal of human genetics	2011	PMID: 21194675
Variable phenotypes associated with 10q23 microdeletions involving the PTEN and BMPR1A genes.	Menko FH	Clinical genetics	2008	PMID: 18510548
Contribution of PTEN large rearrangements in Cowden disease: a multiplex amplifiable probe hybridisation (MAPH) screening approach.	Chibon F	Journal of medical genetics	2008	PMID: 18456716
Contiguous gene deletion within chromosome arm 10q is associated with juvenile polyposis of infancy, reflecting cooperation between the BMPR1A and PTEN tumor-suppressor genes.	Delnatte C	American journal of human genetics	2006	PMID: 16685657
Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis.	Sweet K	JAMA	2005	PMID: 16287957
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.	Marsh DJ	Human molecular genetics	1998	PMID: 9467011
Deletion of PTEN in a patient with Bannayan-Riley-Ruvalcaba syndrome suggests allelism with Cowden disease.	Arch EM	American journal of medical genetics	1997	PMID: 9286463
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Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NC_000010.11:g.(?_86755016)_(87965564_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...