rs934328

Positions:

• chr3-30666252-G-A
• chr3-30666252-G-C
• chr3-30666252-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003242.6(TGFBR2):​c.455-5386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 151,936 control chromosomes in the GnomAD database, including 31,737 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (31737 hom., cov: 31)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910

Genes affected

TGFBR2 (HGNC:11773): (transforming growth factor beta receptor 2) The protein encoded by this gene is a transmembrane protein that has a protein kinase domain, forms a heterodimeric complex with TGF-beta receptor type-1, and binds TGF-beta. This receptor/ligand complex phosphorylates proteins, which then enter the nucleus and regulate the transcription of genes related to cell proliferation, cell cycle arrest, wound healing, immunosuppression, and tumorigenesis. Mutations in this gene have been associated with Marfan Syndrome, Loeys-Deitz Aortic Aneurysm Syndrome, and the development of various types of tumors. Alternatively spliced transcript variants encoding different isoforms have been characterized. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.455-5386G>A		intron_variant		ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.455-5386G>A		intron_variant		1	NM_003242.6	ENSP00000295754.5
TGFBR2	ENST00000359013.4	c.530-5386G>A		intron_variant		1		ENSP00000351905.4
TGFBR2	ENST00000672866.1	n.2051-5386G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97125 AN: 151816 Hom.: 31715 Cov.: 31

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.640 AC: 97201 AN: 151936 Hom.: 31737 Cov.: 31 AF XY: 0.636 AC XY: 47259 AN XY: 74300

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.657

Alfa AF: 0.682 Hom.: 8716

Bravo AF: 0.637

Asia WGS AF: 0.450 AC: 1565 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.71
DANN	Benign	0.55

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: rs934328; hg19: chr3-30707744;