rs3773649

Variant names:

• chr3-30675110-G-A
• rs3773649
• NM_003242.6:c.1396+864G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-30675110-G-A
• chr3-30675110-G-C

Variant summary

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

The NM_003242.6(TGFBR2):​c.1396+864G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,986 control chromosomes in the GnomAD database, including 5,552 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 0.27 (5552 hom., cov: 31)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 19 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.1396+864G>A		intron_variant	Intron 5 of 6	ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.1396+864G>A		intron_variant	Intron 5 of 6	1	NM_003242.6	ENSP00000295754.5

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40285 AN: 151866 Hom.: 5552 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.265 AC: 40302 AN: 151986 Hom.: 5552 Cov.: 31 AF XY: 0.261 AC XY: 19383 AN XY: 74314

African (AFR) AF: 0.202 AC: 8372 AN: 41442

American (AMR) AF: 0.349 AC: 5334 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 723 AN: 3466

East Asian (EAS) AF: 0.316 AC: 1634 AN: 5164

South Asian (SAS) AF: 0.217 AC: 1046 AN: 4822

European-Finnish (FIN) AF: 0.251 AC: 2648 AN: 10550

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19551 AN: 67970

Other (OTH) AF: 0.267 AC: 563 AN: 2108

Alfa AF: 0.285 Hom.: 28801

Bravo AF: 0.276

Asia WGS AF: 0.259 AC: 903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.89
DANN	Benign	0.59
PhyloP100		0.15
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: rs3773649; hg19: chr3-30716602;