rs2005061

Variant names:

• chr3-30649256-G-A
• rs2005061
• NM_003242.6:c.264-1014G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-30649256-G-A
• chr3-30649256-G-C
• chr3-30649256-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.264-1014G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,184 control chromosomes in the GnomAD database, including 1,716 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 0.14 (1716 hom., cov: 32)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.264-1014G>A		intron_variant	Intron 2 of 6	ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.264-1014G>A		intron_variant	Intron 2 of 6	1	NM_003242.6	ENSP00000295754.5

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21049 AN: 152066 Hom.: 1719 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.138 AC: 21058 AN: 152184 Hom.: 1716 Cov.: 32 AF XY: 0.140 AC XY: 10438 AN XY: 74400

African (AFR) AF: 0.109 AC: 4520 AN: 41528

American (AMR) AF: 0.199 AC: 3046 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 390 AN: 3466

East Asian (EAS) AF: 0.375 AC: 1936 AN: 5158

South Asian (SAS) AF: 0.191 AC: 923 AN: 4822

European-Finnish (FIN) AF: 0.111 AC: 1179 AN: 10594

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8467 AN: 68006

Other (OTH) AF: 0.140 AC: 297 AN: 2114

Alfa AF: 0.139 Hom.: 2108

Bravo AF: 0.148

Asia WGS AF: 0.266 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.027
DANN	Benign	0.40
PhyloP100		-1.6
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: rs2005061; hg19: chr3-30690748;