rs749794

Variant names:

• chr3-30666940-G-A
• rs749794
• NM_003242.6:c.455-4698G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-30666940-G-A
• chr3-30666940-G-C
• chr3-30666940-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003242.6(TGFBR2):​c.455-4698G>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 151,738 control chromosomes in the GnomAD database, including 31,734 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 (31734 hom., cov: 30)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 9 publications found

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]

TGFBR2 Gene-Disease associations (from GenCC):

• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Loeys-Dietz syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, G2P
• Loeys-Dietz syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• 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 rank	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.455-4698G>A		intron_variant	Intron 3 of 6	ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.455-4698G>A		intron_variant	Intron 3 of 6	1	NM_003242.6	ENSP00000295754.5

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97081 AN: 151620 Hom.: 31714 Cov.: 30

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.564

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: 97154 AN: 151738 Hom.: 31734 Cov.: 30 AF XY: 0.637 AC XY: 47178 AN XY: 74118

African (AFR) AF: 0.572 AC: 23644 AN: 41330

American (AMR) AF: 0.672 AC: 10241 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2478 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1566 AN: 5132

South Asian (SAS) AF: 0.565 AC: 2720 AN: 4812

European-Finnish (FIN) AF: 0.654 AC: 6882 AN: 10524

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47615 AN: 67904

Other (OTH) AF: 0.656 AC: 1385 AN: 2110

Alfa AF: 0.676 Hom.: 95402

Bravo AF: 0.637

Asia WGS AF: 0.450 AC: 1567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.2
DANN	Benign	0.78
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs749794; hg19: chr3-30708432;