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NM_000314.8(PTEN):c.802-2A>T AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 23, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000131528.10

Allele description [Variation Report for NM_000314.8(PTEN):c.802-2A>T]

NM_000314.8(PTEN):c.802-2A>T

Gene:
PTEN:phosphatase and tensin homolog [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q23.31
Genomic location:
Preferred name:
NM_000314.8(PTEN):c.802-2A>T
HGVS:
  • NC_000010.11:g.87960892A>T
  • NG_007466.2:g.102454A>T
  • NM_000314.8:c.802-2A>TMANE SELECT
  • NM_001304717.5:c.1322-2A>T
  • NM_001304718.2:c.211-2A>T
  • LRG_311t1:c.802-2A>T
  • LRG_311:g.102454A>T
  • NC_000010.10:g.89720649A>T
  • NM_000314.4:c.802-2A>T
  • NM_000314.6:c.802-2A>T
Links:
dbSNP: rs587782455
NCBI 1000 Genomes Browser:
rs587782455
Molecular consequence:
  • NM_000314.8:c.802-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001304717.5:c.1322-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001304718.2:c.211-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000186522Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(May 23, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

KLLN epigenotype-phenotype associations in Cowden syndrome.

Nizialek EA, Mester JL, Dhiman VK, Smiraglia DJ, Eng C.

Eur J Hum Genet. 2015 Nov;23(11):1538-43. doi: 10.1038/ejhg.2015.8. Epub 2015 Feb 11.

PubMed [citation]
PMID:
25669429
PMCID:
PMC4613489

Characterization of cryptic splicing in germline PTEN intronic variants in Cowden syndrome.

Chen HJ, Romigh T, Sesock K, Eng C.

Hum Mutat. 2017 Oct;38(10):1372-1377. doi: 10.1002/humu.23288. Epub 2017 Jul 17.

PubMed [citation]
PMID:
28677221
PMCID:
PMC5599331

Details of each submission

From Ambry Genetics, SCV000186522.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The c.802-2A>T intronic pathogenic mutation results from an A to T substitution two nucleotides upstream from coding exon 8 in the PTEN gene. This alteration segregated with disease in one PTEN hamartoma tumor syndrome (PHTS) family tested at our laboratory (Ambry internal data). This mutation has also been detected in cohorts of patients who met clinical diagnostic criteria for Cowden syndrome (CS) or relaxed clinical diagnostic criteria for CS-like (Nizialek EA et al. Eur. J. Hum. Genet. 2015 Nov;23:1538-43; Chen HJ et al. Hum. Mutat., 2017 10;38:1372-1377). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. RNA studies have demonstrated that this variant results in abnormal splicing with out-of-frame deletion of 43 nucleotides from the beginning of coding exon 8 through use of a cryptic acceptor site (Ambry internal data; Chen HJ et al. Hum. Mutat., 2017 10;38:1372-1377). As such, this alteration is classified as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024