chr10-87863299-C-T
Variant summary
Our verdict is Uncertain significance. Variant got -1 ACMG points: 0P and 1B. BP5
This summary comes from the ClinGen Evidence Repository: PTEN c.-1170C>T (NC_000010.10: g.89623056C>T) is currently classified as a variant of uncertain significance for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (Mester et al. 2018; manuscript in preparation). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column).BP5: Variant found in multiple cases with alternate molecular basis for disease. (Internal laboratory contributor(s) SCV000149466.6, SCV000184146.1) LINK:https://erepo.genome.network/evrepo/ui/classification/CA151481/MONDO:0017623/003
Frequency
Consequence
NM_001126049.2 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLLN | NM_001126049.2 | c.-812G>A | 5_prime_UTR_variant | 1/1 | ENST00000445946.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLLN | ENST00000445946.5 | c.-812G>A | 5_prime_UTR_variant | 1/1 | NM_001126049.2 | P1 | |||
PTEN | ENST00000688308.1 | c.-17+186C>T | intron_variant | P1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152252Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000988 AC: 11AN: 111296Hom.: 0 Cov.: 0 AF XY: 0.0000552 AC XY: 3AN XY: 54376
GnomAD4 genome AF: 0.000118 AC: 18AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74386
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Nov 08, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | PTEN: BP5, BS1 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 15, 2021 | Also known as c.-1170C>T; Observed in at least three individuals, two of whom were reported to have a history of breast and/or thyroid cancer; however, the proband either did not meet full International Cowden Syndrome Consortium operational diagnostic criteria or details were not provided on their specific features (Tan 2011, Wang 2011, Nizialek 2015); No data available from control populations to assess the frequency of this variant; Observed in multiple individuals referred for genetic testing at GeneDx who had a different genetic etiology for the phenotype; This variant is associated with the following publications: (PMID: 21532617, 21194675, 30311380, 25669429) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 13, 2018 | - - |
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. | May 23, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 05, 2014 | - - |
Cowden syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Nov 25, 2015 | - - |
PTEN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 18, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
PTEN hamartoma tumor syndrome Benign:1
Likely benign, reviewed by expert panel | curation | Clingen PTEN Variant Curation Expert Panel, Clingen | Mar 23, 2020 | PTEN c.-1170C>T (NC_000010.10:g. 89623056C>T) meets criteria to be classified as likely 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). BS1_P: Allele frequency of 0.0002477 (0.02477%, 16/64,586 alleles) in the European subpopulation of the gnomAD cohort. (PMID 27535533) BP5: Variant found in multiple cases with alternate molecular basis for disease. (Internal laboratory contributor(s) SCV000149466.6, SCV000184146.1) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at