rs1114167625
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PS4_Supporting
This summary comes from the ClinGen Evidence Repository: PTEN c.39_41del (p.Arg15del) is currently classified as a variant of uncertain significance 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).PM2: Absent in large sequenced populations (PMID 27535533).PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 30528446) LINK:https://erepo.genome.network/evrepo/ui/classification/CA645369492/MONDO:0017623/003
Frequency
Consequence
NM_000314.8 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.39_41del | p.Arg15del | inframe_deletion | 1/9 | ENST00000371953.8 | |
PTEN | NM_001304717.5 | c.558_560del | p.Arg188del | inframe_deletion | 2/10 | ||
PTEN | NM_001304718.2 | c.-667_-665del | 5_prime_UTR_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.39_41del | p.Arg15del | inframe_deletion | 1/9 | 1 | NM_000314.8 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
PTEN hamartoma tumor syndrome Pathogenic:1Uncertain:1
Uncertain significance, reviewed by expert panel | curation | Clingen PTEN Variant Curation Expert Panel, Clingen | Jun 04, 2021 | PTEN c.39_41del (p.Arg15del) is currently classified as a variant of uncertain significance 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). PM2: Absent in large sequenced populations (PMID 27535533). PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 30528446) - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 14, 2023 | This variant, c.39_41del, results in the deletion of 1 amino acid(s) of the PTEN protein (p.Arg15del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of Cowden syndrome (PMID: 25669429, 30528446). ClinVar contains an entry for this variant (Variation ID: 428199). This variant disrupts a region of the PTEN protein in which other variant(s) (p.Arg15Ser) have been determined to be pathogenic (PMID: 16773562, 17942903, 21417916, 21659347, 25875300, 29706350; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 24, 2013 | ​The c.39_41delAAG variant is located in coding exon 1 of the PTEN gene. This variant results from an in-frame 3 base pair deletion between nucleotide positions 39 and 41.This results in the deletion of the arginine residue at codon 14.This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 14,000 alleles tested) in our clinical cohort (includes this individual). Based on sequence alignment,these nucleotide positions andthis amino acid position are highly conserved in available vertebrate species.An in-frame deletion of the adjacent arginine at codon 15 has been reportedin an individual meeting relaxed CS operational criteria (pathognomonic criteria, or at least two major or minor criteria) (Tan, MH et al. Am J Hum Genet. 2011 Jan 7;88(1):42-56). Based on the majority of available evidence to date, this variant is likely to be pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at