10-87931034-CT-C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP6
The NM_000314.8(PTEN):c.210-8delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,222 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). The gene PTEN is included in the ClinGen Criteria Specification Registry.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
PTEN
NM_000314.8 splice_region, intron
NM_000314.8 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.79
Publications
1 publications found
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 Gene-Disease associations (from GenCC):
- Cowden syndrome 1Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
- PTEN hamartoma tumor syndromeInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- macrocephaly-autism syndromeInheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet
- renal cell carcinomaInheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
- leiomyosarcomaInheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
- activated PI3K-delta syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Bannayan-Riley-Ruvalcaba syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Cowden diseaseInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Lhermitte-Duclos diseaseInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Proteus-like syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- glioma susceptibility 2Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
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ACMG classification
Specifications for PTEN are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 10-87931034-CT-C is Benign according to our data. Variant chr10-87931034-CT-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 427626.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000314.8. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000401 AC: 1AN: 249434 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
249434
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.91e-7 AC: 1AN: 1446222Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 720176 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1446222
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
720176
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33104
American (AMR)
AF:
AC:
1
AN:
44464
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25828
East Asian (EAS)
AF:
AC:
0
AN:
39362
South Asian (SAS)
AF:
AC:
0
AN:
85830
European-Finnish (FIN)
AF:
AC:
0
AN:
53192
Middle Eastern (MID)
AF:
AC:
0
AN:
5668
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1099048
Other (OTH)
AF:
AC:
0
AN:
59726
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
-
1
-
Cowden syndrome 1 (1)
-
1
-
Hereditary cancer-predisposing syndrome (1)
-
1
-
not specified (1)
-
-
1
PTEN hamartoma tumor syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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