rs1553631704
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1
The NM_003242.6(TGFBR2):c.1436G>A(p.Arg479Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R479W) has been classified as Uncertain significance.
Frequency
Consequence
NM_003242.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFBR2 | NM_003242.6 | c.1436G>A | p.Arg479Gln | missense_variant | 6/7 | ENST00000295754.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFBR2 | ENST00000295754.10 | c.1436G>A | p.Arg479Gln | missense_variant | 6/7 | 1 | NM_003242.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461838Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727224
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2023 | The p.R479Q variant (also known as c.1436G>A), located in coding exon 6 of the TGFBR2 gene, results from a G to A substitution at nucleotide position 1436. The arginine at codon 479 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 479 of the TGFBR2 protein (p.Arg479Gln). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TGFBR2 protein function. ClinVar contains an entry for this variant (Variation ID: 477540). This variant has not been reported in the literature in individuals affected with TGFBR2-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Malignant tumor of esophagus;C1860896:Colorectal cancer, hereditary nonpolyposis, type 6;C2674574:Loeys-Dietz syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 20, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 06, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# VCV000477540.4); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23913824) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at