3-30672350-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_003242.6(TGFBR2):c.1167C>T(p.Asn389Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,613,836 control chromosomes in the GnomAD database, including 3,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.036 ( 365 hom., cov: 32)
Exomes 𝑓: 0.030 ( 2760 hom. )
Consequence
TGFBR2
NM_003242.6 synonymous
NM_003242.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.87
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
Variant 3-30672350-C-T is Benign according to our data. Variant chr3-30672350-C-T is described in ClinVar as [Benign]. Clinvar id is 44652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-30672350-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-3.87 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TGFBR2 | NM_003242.6 | c.1167C>T | p.Asn389Asn | synonymous_variant | 4/7 | ENST00000295754.10 | NP_003233.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TGFBR2 | ENST00000295754.10 | c.1167C>T | p.Asn389Asn | synonymous_variant | 4/7 | 1 | NM_003242.6 | ENSP00000295754.5 | ||
TGFBR2 | ENST00000359013.4 | c.1242C>T | p.Asn414Asn | synonymous_variant | 5/8 | 1 | ENSP00000351905.4 | |||
TGFBR2 | ENST00000672866.1 | n.2763C>T | non_coding_transcript_exon_variant | 4/7 |
Frequencies
GnomAD3 genomes AF: 0.0361 AC: 5499AN: 152164Hom.: 365 Cov.: 32
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GnomAD3 exomes AF: 0.0550 AC: 13784AN: 250540Hom.: 1253 AF XY: 0.0568 AC XY: 7692AN XY: 135358
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GnomAD4 exome AF: 0.0297 AC: 43365AN: 1461554Hom.: 2760 Cov.: 34 AF XY: 0.0321 AC XY: 23361AN XY: 727062
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GnomAD4 genome AF: 0.0361 AC: 5500AN: 152282Hom.: 365 Cov.: 32 AF XY: 0.0410 AC XY: 3055AN XY: 74454
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ClinVar
Significance: Benign
Submissions summary: Benign:13
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 29, 2007 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 25, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 27, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:2
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 15, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Loeys-Dietz syndrome 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Oct 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Marfan syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Loeys-Dietz syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 19, 2015 | General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance - |
Thoracic aortic aneurysm Benign:1
Benign, no assertion criteria provided | clinical testing | Cohesion Phenomics | Sep 23, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at