Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000548.5(TSC2):c.337-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar 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 (BayesDel_noAF=-0.83).
BP6
Variant 16-2054293-T-C is Benign according to our data. Variant chr16-2054293-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 468009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Likely benign, criteria provided, single submitter
clinical testing
Genome-Nilou Lab
Nov 07, 2021
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Benign, criteria provided, single submitter
clinical testing
Invitae
Nov 10, 2023
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Tuberous sclerosis syndrome Benign:1
Likely benign, criteria provided, single submitter
clinical testing
All of Us Research Program, National Institutes of Health
Apr 28, 2023
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not provided Benign:1
Likely benign, criteria provided, single submitter
clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Mar 28, 2022
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Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter
clinical testing
Ambry Genetics
Jan 25, 2024
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. -