chr3-30694445-G-A

Variant names:

• chr3-30694445-G-A
• rs744751
• ENST00000714390.1:c.*2846G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000714390.1(TGFBR2):​c.*2846G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,070 control chromosomes in the GnomAD database, including 4,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4773 hom., cov: 32)
• Consequence: TGFBR2 ENST00000714390.1 downstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.07
• 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 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 3-30694445-G-A is Benign according to our data. Variant chr3-30694445-G-A is described in ClinVar as Benign. ClinVar VariationId is 1170531.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000714390.1	c.*2846G>A		downstream_gene_variant				ENSP00000519657.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34497 AN: 151952 Hom.: 4777 Cov.: 32

Gnomad AFR AF: 0.0960

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0946

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.227 AC: 34486 AN: 152070 Hom.: 4773 Cov.: 32 AF XY: 0.228 AC XY: 16914 AN XY: 74308

African (AFR) AF: 0.0959 AC: 3981 AN: 41524

American (AMR) AF: 0.151 AC: 2311 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3470

East Asian (EAS) AF: 0.0942 AC: 488 AN: 5178

South Asian (SAS) AF: 0.170 AC: 818 AN: 4822

European-Finnish (FIN) AF: 0.397 AC: 4187 AN: 10548

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21466 AN: 67938

Other (OTH) AF: 0.212 AC: 446 AN: 2104

Alfa AF: 0.278 Hom.: 26252

Bravo AF: 0.203

Asia WGS AF: 0.143 AC: 498 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0080
DANN	Benign	0.41
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs744751; hg19: chr3-30735937;