Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000548.5(TSC2):c.4107G>C(p.Arg1369Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,612,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R1369R) 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]
TSC2 Gene-Disease associations (from GenCC):
tuberous sclerosis
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
tuberous sclerosis 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Ambry Genetics
lymphangioleiomyomatosis
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
tuberous sclerosis complex
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Our verdict: Benign. The variant received -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 16-2084329-G-C is Benign according to our data. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2084329-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 413698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.17 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000788 (12/152206) while in subpopulation AMR AF = 0.000785 (12/15290). AF 95% confidence interval is 0.000452. There are 0 homozygotes in GnomAd4. There are 9 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
Jan 06, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Hereditary cancer-predisposing syndromeBenign:2
Aug 02, 2019
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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. -
Dec 23, 2021
Sema4, Sema4
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:curation
- -
not specifiedBenign:1
Oct 16, 2023
Athena Diagnostics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Lymphangiomyomatosis;C1846385:Isolated focal cortical dysplasia type II;C1860707:Tuberous sclerosis 2Benign:1