rs1346907

Variant names:

• chr3-30681978-A-G
• rs1346907
• NM_003242.6:c.1397-6406A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-30681978-A-G
• chr3-30681978-A-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.1397-6406A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,150 control chromosomes in the GnomAD database, including 28,830 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 0.61 (28830 hom., cov: 33)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.1397-6406A>G		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.1397-6406A>G		intron_variant	Intron 5 of 6	1	NM_003242.6	ENSP00000295754.5

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92365 AN: 152032 Hom.: 28775 Cov.: 33

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.608 AC: 92464 AN: 152150 Hom.: 28830 Cov.: 33 AF XY: 0.611 AC XY: 45439 AN XY: 74384

African (AFR) AF: 0.748 AC: 31050 AN: 41518

American (AMR) AF: 0.598 AC: 9160 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1571 AN: 3472

East Asian (EAS) AF: 0.661 AC: 3413 AN: 5160

South Asian (SAS) AF: 0.542 AC: 2616 AN: 4824

European-Finnish (FIN) AF: 0.624 AC: 6598 AN: 10570

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36354 AN: 67980

Other (OTH) AF: 0.539 AC: 1139 AN: 2112

Alfa AF: 0.556 Hom.: 80871

Bravo AF: 0.613

Asia WGS AF: 0.602 AC: 2092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.083
DANN	Benign	0.52
PhyloP100		-2.3
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: rs1346907; hg19: chr3-30723470;