Variant chr1-218346056-G-GCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003238.6(TGFB2):c.-622_-621dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 145,556 control chromosomes in the GnomAD database, including 117 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.032 ( 117 hom., cov: 28)

Consequence

TGFB2
NM_003238.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.715

Variant links:

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]

TGFB2 links:

TGFB2-AS1 (HGNC:50628): (TGFB2 antisense RNA 1 (head to head))

TGFB2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
TGFB2	NM_003238.6 linkuse as main transcript	c.-622_-621dup	5_prime_UTR_variant	1/7	ENST00000366930.9	NP_003229.1
TGFB2	NM_001135599.4 linkuse as main transcript	c.-622_-621dup	5_prime_UTR_variant	1/8		NP_001129071.1
TGFB2	NR_138148.2 linkuse as main transcript	n.745_746dup	non_coding_transcript_exon_variant	1/7
TGFB2	NR_138149.2 linkuse as main transcript	n.745_746dup	non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFB2	ENST00000366930.9 linkuse as main transcript	c.-622_-621dup	5_prime_UTR_variant	1/7	1	NM_003238.6	ENSP00000355897	P1	P61812-1
TGFB2-AS1	ENST00000689961.2 linkuse as main transcript		upstream_gene_variant
TGFB2-AS1	ENST00000414452.2 linkuse as main transcript		upstream_gene_variant		3
TGFB2-AS1	ENST00000691401.1 linkuse as main transcript		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0315

AC:

4588

AN:

145482

Hom.:

116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0599

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.0612

Gnomad EAS

AF:

0.0152

Gnomad SAS

AF:

0.0787

Gnomad FIN

AF:

0.00864

Gnomad MID

AF:

0.0292

Gnomad NFE

AF:

0.0174

Gnomad OTH

AF:

0.0267

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0316

AC:

4604

AN:

145556

Hom.:

117

Cov.:

AF XY:

0.0326

AC XY:

2307

AN XY:

70874

show subpopulations

Gnomad4 AFR

AF:

0.0601

Gnomad4 AMR

AF:

0.0204

Gnomad4 ASJ

AF:

0.0612

Gnomad4 EAS

AF:

0.0150

Gnomad4 SAS

AF:

0.0792

Gnomad4 FIN

AF:

0.00864

Gnomad4 NFE

AF:

0.0174

Gnomad4 OTH

AF:

0.0281

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Loeys-Dietz syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.