chr16-2057146-C-T
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.816C>T(p.Ala272Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,434 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. A272A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
TSC2
NM_000548.5 synonymous
NM_000548.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.604
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=-0.5).
BP6
Variant 16-2057146-C-T is Benign according to our data. Variant chr16-2057146-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1096779.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.604 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.816C>T | p.Ala272Ala | synonymous | Exon 9 of 42 | NP_000539.2 | ||
| TSC2 | NM_001406663.1 | c.816C>T | p.Ala272Ala | synonymous | Exon 9 of 42 | NP_001393592.1 | |||
| TSC2 | NM_001114382.3 | c.816C>T | p.Ala272Ala | synonymous | Exon 9 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.816C>T | p.Ala272Ala | synonymous | Exon 9 of 42 | ENSP00000219476.3 | ||
| TSC2 | ENST00000350773.9 | TSL:1 | c.816C>T | p.Ala272Ala | synonymous | Exon 9 of 41 | ENSP00000344383.4 | ||
| TSC2 | ENST00000401874.7 | TSL:1 | c.816C>T | p.Ala272Ala | synonymous | Exon 9 of 40 | ENSP00000384468.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000143 AC: 2AN: 1399434Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1AN XY: 690234 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1399434
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
690234
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31600
American (AMR)
AF:
AC:
0
AN:
35724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25182
East Asian (EAS)
AF:
AC:
0
AN:
35742
South Asian (SAS)
AF:
AC:
1
AN:
79268
European-Finnish (FIN)
AF:
AC:
0
AN:
49202
Middle Eastern (MID)
AF:
AC:
0
AN:
5670
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1079034
Other (OTH)
AF:
AC:
0
AN:
58012
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
Significance:Likely 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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