1-218443709-GTT-G

Position:

• chr1-218443709-GTT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000366930.9(TGFB2):​c.*2360_*2361del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (5662 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: TGFB2 ENST00000366930.9 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.47

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-OT1 (HGNC:50629): (TGFB2 overlapping transcript 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-218443709-GTT-G is Benign according to our data. Variant chr1-218443709-GTT-G is described in ClinVar as [Benign]. Clinvar id is 295530.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFB2	NM_003238.6	c.*2360_*2361del		3_prime_UTR_variant	7/7	ENST00000366930.9	NP_003229.1
TGFB2-OT1	NR_125715.1	n.1097_1098del		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFB2	ENST00000366930.9	c.*2360_*2361del		3_prime_UTR_variant	7/7	1	NM_003238.6	ENSP00000355897	P1
TGFB2	ENST00000366929.4	c.*2360_*2361del		3_prime_UTR_variant	8/8	1		ENSP00000355896
TGFB2-OT1	ENST00000625474.1	n.1097_1098del		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 39320 AN: 134886 Hom.: 5652 Cov.: 0

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.276

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.292 AC: 39342 AN: 134936 Hom.: 5662 Cov.: 0 AF XY: 0.294 AC XY: 19142 AN XY: 65068

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.282

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Loeys-Dietz syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3054943; hg19: chr1-218617051;