rs557364463

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: PTEN c.802-51_802-14del (IVS7-51_IVS7-14del) meets criteria to be classified as benign 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).BA1: Allele frequency of 0.01931 (1.931%, 2747/142,290 alleles) in the global gnomAD cohort. (PMID 27535533) LINK:https://erepo.genome.network/evrepo/ui/classification/CA338721/MONDO:0017623/003

Frequency

Genomes: 𝑓 0.018 ( 91 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 6 hom. )

Failed GnomAD Quality Control

Consequence

PTEN
NM_000314.8 intron

Scores

Not classified

Clinical Significance

Benign reviewed by expert panel U:1B:11

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

PTEN (HGNC:9588): (phosphatase and tensin homolog) This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]

PTEN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PTEN	NM_000314.8 link	c.802-51_802-14delAATTAAATATGTCATTTCATTTCTTTTTCTTTTCTTTT	intron_variant	Intron 7 of 8	ENST00000371953.8	NP_000305.3
PTEN	NM_001304717.5 link	c.1321-51_1321-14delAATTAAATATGTCATTTCATTTCTTTTTCTTTTCTTTT	intron_variant	Intron 8 of 9		NP_001291646.4	P60484
PTEN	NM_001304718.2 link	c.211-51_211-14delAATTAAATATGTCATTTCATTTCTTTTTCTTTTCTTTT	intron_variant	Intron 7 of 8		NP_001291647.1	P60484

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTEN	ENST00000371953.8 link	c.802-53_802-16delTTAATTAAATATGTCATTTCATTTCTTTTTCTTTTCTT		intron_variant	Intron 7 of 8	1	NM_000314.8	ENSP00000361021.3		P60484-1

Frequencies

GnomAD3 genomes

AF:

0.0182

AC:

2758

AN:

151158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00844

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0139

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00166

AC:

2244

AN:

1354456

Hom.:

AF XY:

0.00145

AC XY:

971

AN XY:

670666

show subpopulations

Gnomad4 AFR exome

AF:

0.0626

Gnomad4 AMR exome

AF:

0.00443

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000685

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000607

Gnomad4 OTH exome

AF:

0.00387

GnomAD4 genome

AF:

0.0182

AC:

2757

AN:

151260

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1282

AN XY:

73914

show subpopulations

Gnomad4 AFR

AF:

0.0625

Gnomad4 AMR

AF:

0.00843

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0138

Alfa

AF:

0.0129

Hom.:

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:11

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:3

Mayo Clinic Laboratories, Mayo Clinic

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 17, 2017

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:3

Feb 03, 2022

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Feb 20, 2020

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 23, 2019

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

PTEN hamartoma tumor syndrome

Benign:2

Mar 23, 2020

Clingen PTEN Variant Curation Expert Panel, Clingen

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: curation

PTEN c.802-51_802-14del (IVS7-51_IVS7-14del) meets criteria to be classified as benign 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). BA1: Allele frequency of 0.01931 (1.931%, 2747/142,290 alleles) in the global gnomAD cohort. (PMID 27535533) -

May 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: flagged submission

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 11986403) -

Cowden syndrome 1

Uncertain:1

May 26, 2017

Cancer Genomic Medicine Translational Research Lab, Cleveland Clinic Genomic Medicine Institute

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

Breast and/or ovarian cancer

Benign:1

May 18, 2022

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over