3-30620836-C-G

Variant names:

• chr3-30620836-C-G
• rs1036095
• NM_003242.6:c.94+13859C>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+13859C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 151,984 control chromosomes in the GnomAD database, including 39,478 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 0.72 (39478 hom., cov: 31)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 26 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, Unknown Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Loeys-Dietz syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003242.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR2	NM_003242.6	MANE Select	c.94+13859C>G		intron	N/A	NP_003233.4
	TGFBR2	NM_001407126.1		c.95-2363C>G		intron	N/A	NP_001394055.1
	TGFBR2	NM_001407127.1		c.94+13859C>G		intron	N/A	NP_001394056.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR2	ENST00000295754.10	TSL:1 MANE Select	c.94+13859C>G		intron	N/A	ENSP00000295754.5	P37173-1
	TGFBR2	ENST00000359013.4	TSL:1	c.95-2363C>G		intron	N/A	ENSP00000351905.4	P37173-2
	TGFBR2	ENST00000941789.1		c.94+13859C>G		intron	N/A	ENSP00000611848.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109134 AN: 151866 Hom.: 39469 Cov.: 31

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.718 AC: 109181 AN: 151984 Hom.: 39478 Cov.: 31 AF XY: 0.716 AC XY: 53169 AN XY: 74272

African (AFR) AF: 0.631 AC: 26128 AN: 41430

American (AMR) AF: 0.780 AC: 11910 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2329 AN: 3472

East Asian (EAS) AF: 0.766 AC: 3958 AN: 5168

South Asian (SAS) AF: 0.611 AC: 2938 AN: 4808

European-Finnish (FIN) AF: 0.764 AC: 8066 AN: 10554

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51453 AN: 67964

Other (OTH) AF: 0.698 AC: 1470 AN: 2106

Alfa AF: 0.740 Hom.: 5202

Bravo AF: 0.721

Asia WGS AF: 0.680 AC: 2364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.11
DANN	Benign	0.66
PhyloP100		-1.5
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: rs1036095; hg19: chr3-30662328;