rs137854273
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000548.5(TSC2):c.4207delG(p.Asp1403ThrfsTer8) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. D1403D) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TSC2
NM_000548.5 frameshift
NM_000548.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.48
Publications
2 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: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, 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: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-2084425-TG-T is Pathogenic according to our data. Variant chr16-2084425-TG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 49287.Status of the report is criteria_provided_single_submitter, 1 stars.
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
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TSC2 | MANE Select | c.4207delG | p.Asp1403ThrfsTer8 | frameshift | Exon 34 of 42 | NP_000539.2 | P49815-1 | ||
| TSC2 | c.4204delG | p.Asp1402ThrfsTer8 | frameshift | Exon 34 of 42 | NP_001393592.1 | A0A2R8Y6C9 | |||
| TSC2 | c.4138delG | p.Asp1380ThrfsTer8 | frameshift | Exon 33 of 41 | NP_001107854.1 | P49815-4 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TSC2 | TSL:5 MANE Select | c.4207delG | p.Asp1403ThrfsTer8 | frameshift | Exon 34 of 42 | ENSP00000219476.3 | P49815-1 | ||
| TSC2 | TSL:1 | c.4138delG | p.Asp1380ThrfsTer8 | frameshift | Exon 33 of 41 | ENSP00000344383.4 | P49815-4 | ||
| TSC2 | TSL:1 | c.4006delG | p.Asp1336ThrfsTer8 | frameshift | Exon 32 of 40 | ENSP00000384468.2 | P49815-5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1458826Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 725622
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1458826
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
725622
African (AFR)
AF:
AC:
0
AN:
33422
American (AMR)
AF:
AC:
0
AN:
44582
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26080
East Asian (EAS)
AF:
AC:
0
AN:
39608
South Asian (SAS)
AF:
AC:
0
AN:
85886
European-Finnish (FIN)
AF:
AC:
0
AN:
51786
Middle Eastern (MID)
AF:
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111388
Other (OTH)
AF:
AC:
0
AN:
60312
GnomAD4 genome
GnomAD4 genome
Cov.:
34
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
not provided (1)
-
-
-
Tuberous sclerosis syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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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