3-30606540-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001407129.1(TGFBR2):c.-65C>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0000072 in 277,774 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 Uncertain risk allele (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000080 ( 0 hom. )
Consequence
TGFBR2
NM_001407129.1 5_prime_UTR
NM_001407129.1 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.60
Publications
0 publications found
Genes affected
TGFBR2 (HGNC:11773): (transforming growth factor beta receptor 2) The protein encoded by this gene is a transmembrane protein that has a protein kinase domain, forms a heterodimeric complex with TGF-beta receptor type-1, and binds TGF-beta. This receptor/ligand complex phosphorylates proteins, which then enter the nucleus and regulate the transcription of genes related to cell proliferation, cell cycle arrest, wound healing, immunosuppression, and tumorigenesis. Mutations in this gene have been associated with Marfan Syndrome, Loeys-Deitz Aortic Aneurysm Syndrome, and the development of various types of tumors. Alternatively spliced transcript variants encoding different isoforms have been characterized. [provided by RefSeq, Aug 2017]
TGFBR2 Gene-Disease associations (from GenCC):
- Loeys-Dietz syndrome 2Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
- familial thoracic aortic aneurysm and aortic dissectionInheritance: Unknown, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- Loeys-Dietz syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.27).
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001407129.1. 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 |
|---|---|---|---|---|---|---|---|---|---|
| TGFBR2 | NM_001407129.1 | c.-65C>T | 5_prime_UTR | Exon 1 of 8 | NP_001394058.1 | ||||
| TGFBR2 | NM_001407132.1 | c.-65C>T | 5_prime_UTR | Exon 1 of 7 | NP_001394061.1 | A0AAQ5BI06 | |||
| TGFBR2 | NM_003242.6 | MANE Select | c.-344C>T | upstream_gene | N/A | NP_003233.4 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TGFBR2 | ENST00000714391.1 | c.-62C>T | 5_prime_UTR | Exon 1 of 8 | ENSP00000519658.1 | A0AAQ5BI03 | |||
| TGFBR2 | ENST00000714389.1 | c.-60C>T | 5_prime_UTR | Exon 1 of 7 | ENSP00000519656.1 | A0AAQ5BI06 | |||
| TGFBR2 | ENST00000714390.1 | c.-65C>T | 5_prime_UTR | Exon 1 of 7 | ENSP00000519657.1 | A0AAQ5BI06 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152052Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152052
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000795 AC: 1AN: 125722Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 60722 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
125722
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
60722
show subpopulations
African (AFR)
AF:
AC:
0
AN:
5006
American (AMR)
AF:
AC:
0
AN:
3586
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
6222
East Asian (EAS)
AF:
AC:
0
AN:
14242
South Asian (SAS)
AF:
AC:
0
AN:
1080
European-Finnish (FIN)
AF:
AC:
0
AN:
6480
Middle Eastern (MID)
AF:
AC:
0
AN:
732
European-Non Finnish (NFE)
AF:
AC:
1
AN:
78998
Other (OTH)
AF:
AC:
0
AN:
9376
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 0.00000658 AC: 1AN: 152052Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74270 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152052
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74270
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41386
American (AMR)
AF:
AC:
0
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5176
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10604
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67998
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Uncertain risk allele
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Diabetic retinopathy (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
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
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.