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NM_000314.8(PTEN):c.1026+1G>A AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 17, 2021
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:
RCV000162423.4

Allele description [Variation Report for NM_000314.8(PTEN):c.1026+1G>A]

NM_000314.8(PTEN):c.1026+1G>A

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.1026+1G>A
HGVS:
  • NC_000010.11:g.87961119G>A
  • NG_007466.2:g.102681G>A
  • NM_000314.8:c.1026+1G>AMANE SELECT
  • NM_001304717.5:c.1546+1G>A
  • NM_001304718.2:c.435+1G>A
  • LRG_311t1:c.1026+1G>A
  • LRG_311:g.102681G>A
  • NC_000010.10:g.89720876G>A
  • NM_000314.4:c.1026+1G>A
  • NM_000314.6:c.1026+1G>A
  • NM_000314.7:c.1026+1G>A
Links:
dbSNP: rs786201041
NCBI 1000 Genomes Browser:
rs786201041
Molecular consequence:
  • NM_000314.8:c.1026+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001304717.5:c.1546+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001304718.2:c.435+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
Functional consequence:
sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071] - Comment(s)

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
SCV000212764Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jul 17, 2021) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

Different splicing defects lead to differential effects downstream of the lipid and protein phosphatase activities of PTEN.

Agrawal S, Pilarski R, Eng C.

Hum Mol Genet. 2005 Aug 15;14(16):2459-68. Epub 2005 Jul 13.

PubMed [citation]
PMID:
16014636

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, Mester J, Peterson C, Yang Y, Chen JL, Rybicki LA, Milas K, Pederson H, Remzi B, Orloff MS, Eng C.

Am J Hum Genet. 2011 Jan 7;88(1):42-56. doi: 10.1016/j.ajhg.2010.11.013. Epub 2010 Dec 30.

PubMed [citation]
PMID:
21194675
PMCID:
PMC3014373
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000212764.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The c.1026+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 8 of the PTEN gene. In one study, RNA analysis showed that this variant led to abnormal splicing with retention of 190 nt from intron 8 and introduction of a stop codon at p.345 that would result in loss of amino acids encompassing exon 9 (Chen HJ et al. Hum Mutat, 2017 10;38:1372-1377). This alteration has been reported in multiple individuals meeting clinical criteria for Cowden syndrome (Agrawal S et al. Hum Mol Genet. 2005 Aug;14(16):2459-68; Tan MH et al. Am. J. Hum. Genet. 2011 Jan; 88(1):42-56; Chen HJ et al. Hum Mutat, 2017 10;38:1372-1377; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In silico splice site analysis predicts that this alteration will weaken the native splice donor site. 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. 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: Sep 16, 2024