rs397516839
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_003242.6(TGFBR2):c.1418C>A(p.Pro473Gln) variant causes a missense 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P473L) has been classified as Uncertain significance.
Frequency
Consequence
NM_003242.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFBR2 | NM_003242.6 | c.1418C>A | p.Pro473Gln | missense_variant | 6/7 | ENST00000295754.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFBR2 | ENST00000295754.10 | c.1418C>A | p.Pro473Gln | missense_variant | 6/7 | 1 | NM_003242.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 03, 2011 | The Pro473Gln variant has not been reported in the literature nor previously ide ntified by our laboratory. Proline (Pro) at amino acid position 473 is highly co nserved across evolutionarily distant species, increasing the likelihood that th e change is pathogenic. However, computational analyses are mixed with PolyPhen2 predicting pathogenicity, while SIFT and AlignGVGD predict this variant would b e benign. These tools have not been validated sufficiently to determine pathogen icity. Additional data is required to fully assess this variant. Therefore, the clinical significance of the Pro473Gln variant cannot be determined at this time . - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at