Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_000548.5(TSC2):c.3491C>T(p.Ala1164Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,612,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1164S) has been classified as Likely benign.
TSC2 (HGNC:12363): (TSC complex subunit 2) This gene is a tumor suppressor gene that encodes the growth inhibitory protein tuberin. Tuberin interacts with hamartin to form the TSC protein complex which functions in the control of cell growth. This TSC protein complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signaling which is a major regulator of anabolic cell growth. Mutations in this gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. [provided by RefSeq, May 2022]
Computational evidence support a benign effect (MetaRNN=0.07627931).
BP6
Variant 16-2080258-C-T is Benign according to our data. Variant chr16-2080258-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 50090.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=6, not_provided=1, Uncertain_significance=1}. Variant chr16-2080258-C-T is described in Lovd as [Likely_benign]. Variant chr16-2080258-C-T is described in Lovd as [Benign]. Variant chr16-2080258-C-T is described in Lovd as [Likely_pathogenic].
Likely benign, criteria provided, single submitter
clinical testing
Genome-Nilou Lab
Nov 07, 2021
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Uncertain significance, criteria provided, single submitter
clinical testing
Baylor Genetics
Aug 24, 2019
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
not provided Benign:3
Likely benign, criteria provided, single submitter
clinical testing
GeneDx
Sep 21, 2020
This variant is associated with the following publications: (PMID: 15798777, 27153395) -
Likely benign, no assertion criteria provided
clinical testing
Clinical Genetics, Academic Medical Center
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Likely benign, criteria provided, single submitter
clinical testing
CeGaT Center for Human Genetics Tuebingen
Dec 01, 2021
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not specified Benign:2
Likely benign, no assertion criteria provided
clinical testing
Genetic Services Laboratory, University of Chicago
Nov 30, 2022
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Benign, no assertion criteria provided
clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
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Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter
clinical testing
Ambry Genetics
Dec 07, 2018
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Likely benign, criteria provided, single submitter
curation
Sema4, Sema4
Jun 03, 2021
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TSC2-related disorder Benign:1
Likely benign, criteria provided, single submitter
clinical testing
PreventionGenetics, part of Exact Sciences
Dec 17, 2021
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). -