3-30687737-G-C

Variant summary

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

The NM_003242.6(TGFBR2):c.1397-647G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,986 control chromosomes in the GnomAD database, including 28,723 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 0.59 (28723 hom., cov: 32)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR2	NM_003242.6	c.1397-647G>C		intron_variant		ENST00000295754.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR2	ENST00000295754.10	c.1397-647G>C		intron_variant		1	NM_003242.6	P1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89940 AN: 151868 Hom.: 28675 Cov.: 32

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.592 AC: 90041 AN: 151986 Hom.: 28723 Cov.: 32 AF XY: 0.594 AC XY: 44094 AN XY: 74260

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.518

Alfa AF: 0.402 Hom.: 1095

Bravo AF: 0.608

Asia WGS AF: 0.528 AC: 1833 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.20
Dann	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9843143; hg19: chr3-30729229;