chr1-218346056-GCA-G
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_003238.6(TGFB2):c.-622_-621del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00768 in 145,156 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0077 ( 5 hom., cov: 28)
Consequence
TGFB2
NM_003238.6 5_prime_UTR
NM_003238.6 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.336
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 -10 ACMG points.
BP6
?
Variant 1-218346056-GCA-G is Benign according to our data. Variant chr1-218346056-GCA-G is described in ClinVar as [Likely_benign]. Clinvar id is 295476.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00768 (1115/145156) while in subpopulation SAS AF= 0.013 (57/4386). AF 95% confidence interval is 0.0103. There are 5 homozygotes in gnomad4. There are 572 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1110 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFB2 | NM_003238.6 | c.-622_-621del | 5_prime_UTR_variant | 1/7 | ENST00000366930.9 | ||
TGFB2 | NM_001135599.4 | c.-622_-621del | 5_prime_UTR_variant | 1/8 | |||
TGFB2 | NR_138148.2 | n.745_746del | non_coding_transcript_exon_variant | 1/7 | |||
TGFB2 | NR_138149.2 | n.745_746del | non_coding_transcript_exon_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFB2 | ENST00000366930.9 | c.-622_-621del | 5_prime_UTR_variant | 1/7 | 1 | NM_003238.6 | P1 | ||
TGFB2-AS1 | ENST00000689961.2 | upstream_gene_variant | |||||||
TGFB2-AS1 | ENST00000414452.2 | upstream_gene_variant | 3 | ||||||
TGFB2-AS1 | ENST00000691401.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00765 AC: 1110AN: 145080Hom.: 5 Cov.: 28
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.00768 AC: 1115AN: 145156Hom.: 5 Cov.: 28 AF XY: 0.00809 AC XY: 572AN XY: 70666
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Loeys-Dietz syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at