chr3-30624960-C-G

Variant names:

• chr3-30624960-C-G
• rs11709624
• NM_003242.6:c.94+17983C>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.94+17983C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,882 control chromosomes in the GnomAD database, including 9,808 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 0.34 (9808 hom., cov: 31)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.94+17983C>G		intron_variant	Intron 1 of 6	ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.94+17983C>G		intron_variant	Intron 1 of 6	1	NM_003242.6	ENSP00000295754.5

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52377 AN: 151764 Hom.: 9816 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.345 AC: 52395 AN: 151882 Hom.: 9808 Cov.: 31 AF XY: 0.349 AC XY: 25921 AN XY: 74216

African (AFR) AF: 0.221 AC: 9140 AN: 41434

American (AMR) AF: 0.391 AC: 5967 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3466

East Asian (EAS) AF: 0.682 AC: 3500 AN: 5130

South Asian (SAS) AF: 0.363 AC: 1747 AN: 4816

European-Finnish (FIN) AF: 0.438 AC: 4613 AN: 10520

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25399 AN: 67936

Other (OTH) AF: 0.352 AC: 742 AN: 2106

Alfa AF: 0.367 Hom.: 1359

Bravo AF: 0.337

Asia WGS AF: 0.496 AC: 1727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.64
PhyloP100		0.25
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: rs11709624; hg19: chr3-30666452;