NM_003242.6:c.1524+1279T>A

Variant names:

• chr3-30689790-T-A
• rs304839
• NM_003242.6:c.1524+1279T>A

Variant summary

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

The NM_003242.6(TGFBR2):​c.1524+1279T>A variant causes a intron change. The variant allele was found at a frequency of 0.86 in 152,304 control chromosomes in the GnomAD database, including 56,744 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 0.86 (56744 hom., cov: 33)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.17
• Publications: 10 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=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.1524+1279T>A		intron_variant	Intron 6 of 6	ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.1524+1279T>A		intron_variant	Intron 6 of 6	1	NM_003242.6	ENSP00000295754.5

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130922 AN: 152186 Hom.: 56682 Cov.: 33

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.860 AC: 131045 AN: 152304 Hom.: 56744 Cov.: 33 AF XY: 0.862 AC XY: 64202 AN XY: 74454

African (AFR) AF: 0.966 AC: 40159 AN: 41586

American (AMR) AF: 0.865 AC: 13243 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2608 AN: 3468

East Asian (EAS) AF: 0.874 AC: 4535 AN: 5188

South Asian (SAS) AF: 0.833 AC: 4020 AN: 4828

European-Finnish (FIN) AF: 0.869 AC: 9213 AN: 10596

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54586 AN: 68014

Other (OTH) AF: 0.832 AC: 1757 AN: 2112

Alfa AF: 0.820 Hom.: 6448

Bravo AF: 0.868

Asia WGS AF: 0.880 AC: 3060 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.82
PhyloP100		4.2
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: rs304839; hg19: chr3-30731282;