NM_003242.6:c.455-670C>G

Variant names:

• chr3-30670968-C-G
• rs3773645
• NM_003242.6:c.455-670C>G

Variant summary

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

The NM_003242.6(TGFBR2):​c.455-670C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,160 control chromosomes in the GnomAD database, including 5,758 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 0.26 (5758 hom., cov: 33)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• Publications: 15 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.455-670C>G		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.455-670C>G		intron_variant	Intron 3 of 6	1	NM_003242.6	ENSP00000295754.5

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39932 AN: 152042 Hom.: 5760 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.262 AC: 39936 AN: 152160 Hom.: 5758 Cov.: 33 AF XY: 0.258 AC XY: 19222 AN XY: 74386

African (AFR) AF: 0.149 AC: 6195 AN: 41512

American (AMR) AF: 0.354 AC: 5409 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3470

East Asian (EAS) AF: 0.317 AC: 1640 AN: 5170

South Asian (SAS) AF: 0.226 AC: 1090 AN: 4832

European-Finnish (FIN) AF: 0.281 AC: 2971 AN: 10574

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20855 AN: 67986

Other (OTH) AF: 0.274 AC: 579 AN: 2114

Alfa AF: 0.273 Hom.: 732

Bravo AF: 0.268

Asia WGS AF: 0.263 AC: 916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.67
PhyloP100		0.32
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: rs3773645; hg19: chr3-30712460;