rs727504406
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_003242.6(TGFBR2):c.464C>T(p.Thr155Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,614,094 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T155T) has been classified as Likely benign.
Frequency
Consequence
NM_003242.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFBR2 | NM_003242.6 | c.464C>T | p.Thr155Ile | missense_variant | 4/7 | ENST00000295754.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFBR2 | ENST00000295754.10 | c.464C>T | p.Thr155Ile | missense_variant | 4/7 | 1 | NM_003242.6 | P1 | |
TGFBR2 | ENST00000359013.4 | c.539C>T | p.Thr180Ile | missense_variant | 5/8 | 1 | |||
TGFBR2 | ENST00000672866.1 | n.2060C>T | non_coding_transcript_exon_variant | 4/7 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000143 AC: 36AN: 251324Hom.: 0 AF XY: 0.000213 AC XY: 29AN XY: 135832
GnomAD4 exome AF: 0.0000691 AC: 101AN: 1461874Hom.: 1 Cov.: 34 AF XY: 0.000102 AC XY: 74AN XY: 727238
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74374
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 11, 2017 | Variant summary: The TGFBR2 c.464C>T (p.Thr155Ile) variant located in the transforming growth ffactor beta receptor 2 ectodomain (via InterPro) involves the alteration of a non-conserved nucleotide and 3/4 in silico tools (SNPsandGO not captured due to low reliability index) predict a benign outcome for this variant. This variant was found in 35/246096 control chromosomes, predominantly observed in the South Asian subpopulation at a frequency of 0.001137 (35/30782). This frequency is about 364 times the estimated maximal expected allele frequency of a pathogenic TGFBR2 variant (0.0000031), suggesting this is likely a benign polymorphism found primarily in population(s) of South Asian origin. A publication, Lerner-Ellis_2014, cites the variant in one affected individual with limited information (no cosegregation data). A clinical diagnostic laboratory classified this variant as uncertain significance, however, this classification occurred prior to the availablity of gnomAD or ExAC. Therefore, the variant of interest has been classified as "benign." - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 24, 2010 | Variant classified as Uncertain Significance - Favor Pathogenic. - |
Familial thoracic aortic aneurysm and aortic dissection Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 08, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 19, 2019 | - - |
Loeys-Dietz syndrome 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Nov 30, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 12, 2019 | See Variant Classification Assertion Criteria. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at