chr1-218346056-G-GCACACACACACACACACA
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2
The NM_003238.6(TGFB2):c.-638_-621dupACACACACACACACACAC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 145,604 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 28)
Consequence
TGFB2
NM_003238.6 5_prime_UTR
NM_003238.6 5_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.715
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 -8 ACMG points.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000117 (17/145604) while in subpopulation AFR AF= 0.000429 (17/39610). AF 95% confidence interval is 0.000273. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
BS2
High AC in GnomAd4 at 17 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TGFB2 | NM_003238.6 | c.-638_-621dupACACACACACACACACAC | 5_prime_UTR_variant | Exon 1 of 7 | ENST00000366930.9 | NP_003229.1 | ||
| TGFB2 | NM_001135599.4 | c.-638_-621dupACACACACACACACACAC | 5_prime_UTR_variant | Exon 1 of 8 | NP_001129071.1 | |||
| TGFB2 | NR_138148.2 | n.729_746dupACACACACACACACACAC | non_coding_transcript_exon_variant | Exon 1 of 7 | ||||
| TGFB2 | NR_138149.2 | n.729_746dupACACACACACACACACAC | non_coding_transcript_exon_variant | Exon 1 of 8 |
Ensembl
Frequencies
GnomAD3 genomes 0.000117 AC: 17AN: 145604Hom.: 0 Cov.: 28
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GnomAD4 genome 0.000117 AC: 17AN: 145604Hom.: 0 Cov.: 28 AF XY: 0.000141 AC XY: 10AN XY: 70864
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ClinVar
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at