NM_000314.8(PTEN):c.802-12T>C AND PTEN hamartoma tumor syndrome

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Feb 5, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001108875.7

Allele description [Variation Report for NM_000314.8(PTEN):c.802-12T>C]

NM_000314.8(PTEN):c.802-12T>C

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.802-12T>C

HGVS:

NC_000010.11:g.87960882T>C
NG_007466.2:g.102444T>C
NM_000314.8:c.802-12T>CMANE SELECT
NM_001304717.5:c.1322-12T>C
NM_001304718.2:c.211-12T>C
LRG_311t1:c.802-12T>C
LRG_311:g.102444T>C
NC_000010.10:g.89720639T>C
NM_000314.4:c.802-12T>C
NM_000314.6:c.802-12T>C

Links:

dbSNP: rs587781129

NCBI 1000 Genomes Browser:

rs587781129

Molecular consequence:

NM_000314.8:c.802-12T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001304717.5:c.1322-12T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001304718.2:c.211-12T>C - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001266162	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV001552018	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Likely benign	unknown	clinical testing
SCV004822641	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Benign (Feb 5, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001266162

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Jan 13, 2018)

germline

clinical testing

Citation Link,

SCV001552018

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided

Likely benign

unknown

clinical testing

SCV004822641

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Benign
(Feb 5, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	42	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001266162.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#	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 Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001552018.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The PTEN c.802-12T>C variant was not identified in the literature nor was it identified in the following databases: Cosmic, MutDB, LOVD 3.0, or Zhejiang Colon Cancer Database. The variant was identified in the databases: dbSNP (ID: rs587781129) as "With Likely benign allele", and ClinVar/Clinvitae (2x, benign/likely benign). The variant was identified in control databases in 51 of 204652 chromosomes at a frequency of 0.0002 increasing the likelihood that this may be a low frequency benign variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017). Of note, in the Ashkenazi Jewish population the variant was identified in 40 of 8652 chromosomes (freq. 0.005). The c.802-12T>C variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. Conversely, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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

From All of Us Research Program, National Institutes of Health, SCV004822641.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	42	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		42	not provided	not provided	not provided

Last Updated: May 16, 2025

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