chr1-218347031-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_003238.6(TGFB2):c.330C>T(p.Pro110=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000377 in 1,591,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
TGFB2
NM_003238.6 synonymous
NM_003238.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.67
Genes affected
TGFB2 (HGNC:11768): (transforming growth factor beta 2) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGF-beta family members. Disruption of the TGF-beta/SMAD pathway has been implicated in a variety of human cancers. A chromosomal translocation that includes this gene is associated with Peters' anomaly, a congenital defect of the anterior chamber of the eye. Mutations in this gene may be associated with Loeys-Dietz syndrome. This gene encodes multiple isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
Variant 1-218347031-C-T is Benign according to our data. Variant chr1-218347031-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 414971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.67 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFB2 | NM_003238.6 | c.330C>T | p.Pro110= | synonymous_variant | 1/7 | ENST00000366930.9 | |
TGFB2 | NM_001135599.4 | c.330C>T | p.Pro110= | synonymous_variant | 1/8 | ||
TGFB2 | NR_138148.2 | n.1696C>T | non_coding_transcript_exon_variant | 1/7 | |||
TGFB2 | NR_138149.2 | n.1696C>T | non_coding_transcript_exon_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFB2 | ENST00000366930.9 | c.330C>T | p.Pro110= | synonymous_variant | 1/7 | 1 | NM_003238.6 | P1 | |
TGFB2 | ENST00000366929.4 | c.330C>T | p.Pro110= | synonymous_variant | 1/8 | 1 | |||
TGFB2 | ENST00000488793.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000498 AC: 1AN: 200796Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 109068
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GnomAD4 exome AF: 0.00000208 AC: 3AN: 1438958Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2AN XY: 713868
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74326
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 22, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Loeys-Dietz syndrome 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at