1-218434160-G-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_003238.6(TGFB2):c.589G>T(p.Glu197*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_003238.6 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TGFB2 | NM_003238.6 | c.589G>T | p.Glu197* | stop_gained | Exon 3 of 7 | ENST00000366930.9 | NP_003229.1 | |
TGFB2 | NM_001135599.4 | c.673G>T | p.Glu225* | stop_gained | Exon 4 of 8 | NP_001129071.1 | ||
TGFB2 | NR_138148.2 | n.1955G>T | non_coding_transcript_exon_variant | Exon 3 of 7 | ||||
TGFB2 | NR_138149.2 | n.2039G>T | non_coding_transcript_exon_variant | Exon 4 of 8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TGFB2 | ENST00000366930.9 | c.589G>T | p.Glu197* | stop_gained | Exon 3 of 7 | 1 | NM_003238.6 | ENSP00000355897.4 | ||
TGFB2 | ENST00000366929.4 | c.673G>T | p.Glu225* | stop_gained | Exon 4 of 8 | 1 | ENSP00000355896.4 | |||
TGFB2 | ENST00000479322.1 | n.35G>T | non_coding_transcript_exon_variant | Exon 1 of 5 | 3 | |||||
TGFB2 | ENST00000488793.1 | n.253G>T | non_coding_transcript_exon_variant | Exon 3 of 3 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Loeys-Dietz syndrome 4 Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. This variant is also known as c.673G>T (p.Glu225*). This premature translational stop signal has been observed in individual(s) with Loeys-Dietz syndrome (PMID: 29392890). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu197*) in the TGFB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TGFB2 are known to be pathogenic (PMID: 22772368, 22772371, 30739908). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.