3-30691909-TTATATATATA-TTATA
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_003242.6(TGFBR2):c.*324_*329delATATAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000808 in 247,402 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000068 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
TGFBR2
NM_003242.6 3_prime_UTR
NM_003242.6 3_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.05
Publications
3 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):
- familial thoracic aortic aneurysm and aortic dissectionInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- Loeys-Dietz syndrome 2Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, G2P
- 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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TGFBR2 | NM_003242.6 | c.*324_*329delATATAT | 3_prime_UTR_variant | Exon 7 of 7 | ENST00000295754.10 | NP_003233.4 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TGFBR2 | ENST00000295754.10 | c.*324_*329delATATAT | 3_prime_UTR_variant | Exon 7 of 7 | 1 | NM_003242.6 | ENSP00000295754.5 |
Frequencies
GnomAD3 genomes 0.00000679 AC: 1AN: 147324Hom.: 0 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
147324
Hom.:
Cov.:
0
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: 0.00000999 AC: 1AN: 100078Hom.: 0 AF XY: 0.0000202 AC XY: 1AN XY: 49606 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
100078
Hom.:
AF XY:
AC XY:
1
AN XY:
49606
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
4062
American (AMR)
AF:
AC:
0
AN:
5250
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
4698
East Asian (EAS)
AF:
AC:
1
AN:
12362
South Asian (SAS)
AF:
AC:
0
AN:
6768
European-Finnish (FIN)
AF:
AC:
0
AN:
1620
Middle Eastern (MID)
AF:
AC:
0
AN:
510
European-Non Finnish (NFE)
AF:
AC:
0
AN:
57870
Other (OTH)
AF:
AC:
0
AN:
6938
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
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 0.00000679 AC: 1AN: 147324Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 71690 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
147324
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
71690
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
39832
American (AMR)
AF:
AC:
0
AN:
14746
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3422
East Asian (EAS)
AF:
AC:
0
AN:
5090
South Asian (SAS)
AF:
AC:
0
AN:
4700
European-Finnish (FIN)
AF:
AC:
0
AN:
9346
Middle Eastern (MID)
AF:
AC:
0
AN:
306
European-Non Finnish (NFE)
AF:
AC:
1
AN:
66970
Other (OTH)
AF:
AC:
0
AN:
2010
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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