NM_000314.8(PTEN):c.801+1del AND PTEN hamartoma tumor syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 23, 2020
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000461085.14

Allele description

NM_000314.8(PTEN):c.801+1del

Gene:

PTEN:phosphatase and tensin homolog [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

10q23.31

Genomic location:

Preferred name:

NM_000314.8(PTEN):c.801+1del

HGVS:

NC_000010.11:g.87958020del
NG_007466.2:g.99582del
NM_000314.8:c.801+1delMANE SELECT
NM_001304717.5:c.1321+1del
NM_001304718.2:c.210+1del
LRG_311t1:c.801+1del
LRG_311:g.99582del
NC_000010.10:g.89717776del
NC_000010.10:g.89717777del
NC_000010.11:g.87958020delG
NM_000314.4:c.801+1del
NM_000314.4:c.801+1delG

Links:

dbSNP: rs1060500110

NCBI 1000 Genomes Browser:

rs1060500110

Molecular consequence:

NM_000314.8:c.801+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001304717.5:c.1321+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001304718.2:c.210+1del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: PTEN hamartoma tumor syndrome (PHTS)
Synonyms:: PTEN Hamartomatous Tumour Syndrome
Identifiers:: MONDO: MONDO:0017623; MeSH: D006223; MedGen: C1959582

Recent activity

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Homo sapiens outer dense fiber of sperm tails 2 like (ODF2L), transcript variant...
Homo sapiens outer dense fiber of sperm tails 2 like (ODF2L), transcript variant 1, mRNA
gi|2067662300|ref|NM_020729.4|

Nucleotide
Homo sapiens SH3 domain binding glutamic acid-rich protein like 2, mRNA (cDNA cl...
Homo sapiens SH3 domain binding glutamic acid-rich protein like 2, mRNA (cDNA clone MGC:125697 IMAGE:40028802), complete cds
gi|133778212|gb|BC109044.2|

Nucleotide
Homo sapiens RuvB-like 2 (E. coli), mRNA (cDNA clone MGC:8354 IMAGE:2819778), co...
Homo sapiens RuvB-like 2 (E. coli), mRNA (cDNA clone MGC:8354 IMAGE:2819778), complete cds
gi|38197149|gb|BC000428.2|

Nucleotide
Vaccinium cylindraceum internal transcribed spacer 1, partial sequence; 5.8S rib...
Vaccinium cylindraceum internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence
gi|30408132|gb|AY274574.1|

Nucleotide
Rattus norvegicus tRNA selenocysteine 1 associated protein 1 (Trnau1ap), mRNA
Rattus norvegicus tRNA selenocysteine 1 associated protein 1 (Trnau1ap), mRNA
gi|12711699|ref|NM_023027.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000541581	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 4, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16199547, 9467011, 21194675, 11238682, 20712882, 28492532
SCV000840487	Clingen PTEN Variant Curation Expert Panel, Clingen	reviewed by expert panel (ClinGen PTEN ACMG Specifications v2)	Pathogenic (Mar 23, 2020)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000541581

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 4, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV000840487

Clingen PTEN Variant Curation Expert Panel, Clingen

reviewed by expert panel

(ClinGen PTEN ACMG Specifications v2)

Pathogenic
(Mar 23, 2020)

germline

curation

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.

Marsh DJ, Coulon V, Lunetta KL, Rocca-Serra P, Dahia PL, Zheng Z, Liaw D, Caron S, Duboué B, Lin AY, Richardson AL, Bonnetblanc JM, Bressieux JM, Cabarrot-Moreau A, Chompret A, Demange L, Eeles RA, Yahanda AM, Fearon ER, Fricker JP, Gorlin RJ, Hodgson SV, et al.

Hum Mol Genet. 1998 Mar;7(3):507-15.

PubMed [citation]

PMID:: 9467011

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000541581.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change affects a splice site in intron 7 of the PTEN gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Cowden syndrome (PMID: 11238682, 20712882; Invitae). This variant is also known as c.802delG. ClinVar contains an entry for this variant (Variation ID: 404140). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clingen PTEN Variant Curation Expert Panel, Clingen, SCV000840487.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

Description

PTEN c.801+1delG (IVS7+1delG) meets criteria to be classified as pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). PVS1: Null variant predicted to result in nonsense-mediated decay or causing truncation/frameshift at or 5' to c.1121 (NM_000314.4). PM2: Absent in large sequenced populations PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 23335809)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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