16-2080286-C-G
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000548.5(TSC2):c.3519C>G(p.Thr1173Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,622 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 Benign (★). Synonymous variant affecting the same amino acid position (i.e. T1173T) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
TSC2
NM_000548.5 synonymous
NM_000548.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.171
Publications
1 publications found
Genes affected
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 sclerosisInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- tuberous sclerosis 2Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Ambry Genetics
- lymphangioleiomyomatosisInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- tuberous sclerosis complexInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 16-2080286-C-G is Benign according to our data. Variant chr16-2080286-C-G is described in ClinVar as Benign. ClinVar VariationId is 2813192.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.171 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000548.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TSC2 | NM_000548.5 | MANE Select | c.3519C>G | p.Thr1173Thr | synonymous | Exon 30 of 42 | NP_000539.2 | ||
| TSC2 | NM_001406663.1 | c.3516C>G | p.Thr1172Thr | synonymous | Exon 30 of 42 | NP_001393592.1 | |||
| TSC2 | NM_001114382.3 | c.3519C>G | p.Thr1173Thr | synonymous | Exon 30 of 41 | NP_001107854.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TSC2 | ENST00000219476.9 | TSL:5 MANE Select | c.3519C>G | p.Thr1173Thr | synonymous | Exon 30 of 42 | ENSP00000219476.3 | ||
| TSC2 | ENST00000350773.9 | TSL:1 | c.3519C>G | p.Thr1173Thr | synonymous | Exon 30 of 41 | ENSP00000344383.4 | ||
| TSC2 | ENST00000401874.7 | TSL:1 | c.3387C>G | p.Thr1129Thr | synonymous | Exon 29 of 40 | ENSP00000384468.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000400 AC: 1AN: 250186 AF XY: 0.00000737 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
250186
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460622Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726606 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460622
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
726606
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
1
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
52196
Middle Eastern (MID)
AF:
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111996
Other (OTH)
AF:
AC:
0
AN:
60378
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions as Germline
Significance:Benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
Tuberous sclerosis 2 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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