rs2043136

Variant names:

• chr3-30678812-G-A
• rs2043136
• NM_003242.6:c.1396+4566G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-30678812-G-A
• chr3-30678812-G-C
• chr3-30678812-G-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.1396+4566G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,034 control chromosomes in the GnomAD database, including 40,774 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 0.73 (40774 hom., cov: 31)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• 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, 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.797 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.1396+4566G>A		intron	N/A	NP_003233.4
	TGFBR2	NM_001407126.1		c.1579+4566G>A		intron	N/A	NP_001394055.1
	TGFBR2	NM_001407127.1		c.1504+4566G>A		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.1396+4566G>A		intron	N/A	ENSP00000295754.5	P37173-1
	TGFBR2	ENST00000359013.4	TSL:1	c.1471+4566G>A		intron	N/A	ENSP00000351905.4	P37173-2
	TGFBR2	ENST00000941789.1		c.1396+4566G>A		intron	N/A	ENSP00000611848.1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111035 AN: 151916 Hom.: 40749 Cov.: 31

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.731 AC: 111114 AN: 152034 Hom.: 40774 Cov.: 31 AF XY: 0.724 AC XY: 53842 AN XY: 74320

African (AFR) AF: 0.710 AC: 29386 AN: 41416

American (AMR) AF: 0.809 AC: 12368 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2441 AN: 3468

East Asian (EAS) AF: 0.570 AC: 2933 AN: 5150

South Asian (SAS) AF: 0.565 AC: 2722 AN: 4816

European-Finnish (FIN) AF: 0.718 AC: 7592 AN: 10580

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51228 AN: 67990

Other (OTH) AF: 0.741 AC: 1567 AN: 2116

Alfa AF: 0.745 Hom.: 179247

Bravo AF: 0.745

Asia WGS AF: 0.592 AC: 2060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.14
PhyloP100		-0.50
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: rs2043136; hg19: chr3-30720304;