This sequence change affects a donor splice site in intron 8 of the PTEN gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Cowden or Cowden-like syndrome and overgrowth and intellectual disability (PMID: 21194675, 28475857, 28677221). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 635377). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
Help
- Interpretation:
-
Pathogenic
- Review status:
- criteria provided, multiple submitters, no conflicts
- Submissions:
- 3
- First in ClinVar:
- Jul 6, 2019
- Most recent Submission:
- Mar 11, 2023
- Last evaluated:
- Apr 2, 2022
- Accession:
- VCV000635377.8
- Variation ID:
- 635377
- Description:
- single nucleotide variant
Help
NM_000314.8(PTEN):c.1026+1G>T
- Allele ID
- 623200
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 10q23.31
- Genomic location
- 10: 87961119 (GRCh38) GRCh38 UCSC
- 10: 89720876 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000314.8:c.1026+1G>T MANE Select splice donor NM_001304717.5:c.1546+1G>T splice donor NM_001304718.2:c.435+1G>T splice donor NC_000010.11:g.87961119G>T NC_000010.10:g.89720876G>T NG_007466.2:g.102681G>T LRG_311:g.102681G>T LRG_311t1:c.1026+1G>T - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000010.11:87961118:G:T
- Functional consequence
- sequence_variant_affecting_splicing [Sequence Ontology SO:1000071]
- Intron inclusion between exons 8 & 9, and loss of exon 9 expression, based on review of RNA-seq in U-118 MG cancer cell line which has PTEN NM_000314.6:c.1026+1G>T variant. [submitted by MutSpliceDB: a database of splice sites variants effects on splicing,NIH]
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- dbSNP: rs786201041
- VarSome
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Pathogenic | 2 | criteria provided, single submitter | Mar 10, 2020 | RCV000786804.3 | |
| Pathogenic | 1 | criteria provided, single submitter | Apr 2, 2022 | RCV001220442.4 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Pathogenic
(Apr 02, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
PTEN hamartoma tumor syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001392431.4
First in ClinVar: Jul 16, 2020 Last updated: Feb 07, 2023 |
Comment:
This sequence change affects a donor splice site in intron 8 of the PTEN gene. While this variant is not anticipated to result in nonsense … (more)
This sequence change affects a donor splice site in intron 8 of the PTEN gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Cowden or Cowden-like syndrome and overgrowth and intellectual disability (PMID: 21194675, 28475857, 28677221). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 635377). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Mar 10, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
PerkinElmer Genomics
Accession: SCV002019541.2
First in ClinVar: Nov 29, 2021 Last updated: Mar 11, 2023 |
|
|
|
not provided
(-)
|
no assertion provided
Method: in vitro
|
not provided
Affected status: not applicable
Allele origin:
not applicable
|
MutSpliceDB: a database of splice sites variants effects on splicing,NIH
Accession: SCV000925696.2
First in ClinVar: Jul 06, 2019 Last updated: Jul 06, 2019 |
Method: Based on review of RNA-seq data in sample with variant.
Result:
Intron inclusion between exons 8 & 9, and loss of exon 9 expression
|
Functional evidence
Help| Functional consequence | Method | Result | Submitter | Supporting information
(See all) |
|---|---|---|---|---|
|
sequence_variant_affecting_splicing
|
|
|
MutSpliceDB: a database of splice sites variants effects on splicing,NIH
Accession: SCV000925696.2
Submitted: (Nov 07, 2019)
|
Comment:
Intron inclusion between exons 8 & 9, and loss of exon 9 expression, based on review of RNA-seq in U-118 MG cancer cell line which … (more)
Intron inclusion between exons 8 & 9, and loss of exon 9 expression, based on review of RNA-seq in U-118 MG cancer cell line which has PTEN NM_000314.6:c.1026+1G>T variant. (less)
|
Citations for this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Characterization of cryptic splicing in germline PTEN intronic variants in Cowden syndrome. | Chen HJ | Human mutation | 2017 | PMID: 28677221 |
| Mutations in Epigenetic Regulation Genes Are a Major Cause of Overgrowth with Intellectual Disability. | Tatton-Brown K | American journal of human genetics | 2017 | PMID: 28475857 |
| 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 | American journal of human genetics | 2011 | PMID: 21194675 |
| Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
| Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
| https://brb.nci.nih.gov/cgi-bin/splicing/splicing_evidence.cgi?caid=CA377486187 | - | - | - | - |
Text-mined citations for rs786201041...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Mar 11, 2023