rs2736627
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000314.8(PTEN):c.1026+219C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 521,718 control chromosomes in the GnomAD database, including 216,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.92 ( 64833 hom., cov: 31)
Exomes 𝑓: 0.91 ( 152085 hom. )
Consequence
PTEN
NM_000314.8 intron
NM_000314.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.893
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 10-87961337-C-T is Benign according to our data. Variant chr10-87961337-C-T is described in ClinVar as [Benign]. Clinvar id is 1245322.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-87961337-C-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.1026+219C>T | intron_variant | ENST00000371953.8 | |||
PTEN | NM_001304717.5 | c.1545+219C>T | intron_variant | ||||
PTEN | NM_001304718.2 | c.436+219C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.1026+219C>T | intron_variant | 1 | NM_000314.8 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.921 AC: 140132AN: 152104Hom.: 64767 Cov.: 31
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GnomAD4 exome AF: 0.906 AC: 334811AN: 369496Hom.: 152085 Cov.: 4 AF XY: 0.908 AC XY: 177769AN XY: 195732
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GnomAD4 genome ? AF: 0.921 AC: 140256AN: 152222Hom.: 64833 Cov.: 31 AF XY: 0.924 AC XY: 68755AN XY: 74416
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 21, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at