3-30613989-A-G

Variant names:

• chr3-30613989-A-G
• rs1835538
• NM_003242.6:c.94+7012A>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+7012A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 152,004 control chromosomes in the GnomAD database, including 28,872 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 0.61 (28872 hom., cov: 31)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 9 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 = 0.847 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR2	NM_003242.6	MANE Select	c.94+7012A>G		intron	N/A	NP_003233.4
	TGFBR2	NM_001407126.1		c.94+7012A>G		intron	N/A	NP_001394055.1
	TGFBR2	NM_001407127.1		c.94+7012A>G		intron	N/A	NP_001394056.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR2	ENST00000295754.10	TSL:1 MANE Select	c.94+7012A>G		intron	N/A	ENSP00000295754.5
	TGFBR2	ENST00000359013.4	TSL:1	c.94+7012A>G		intron	N/A	ENSP00000351905.4
	TGFBR2	ENST00000714391.1		c.-9+7396A>G		intron	N/A	ENSP00000519658.1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92068 AN: 151886 Hom.: 28841 Cov.: 31

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.606 AC: 92164 AN: 152004 Hom.: 28872 Cov.: 31 AF XY: 0.613 AC XY: 45542 AN XY: 74304

African (AFR) AF: 0.743 AC: 30813 AN: 41460

American (AMR) AF: 0.525 AC: 8021 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1741 AN: 3464

East Asian (EAS) AF: 0.868 AC: 4493 AN: 5178

South Asian (SAS) AF: 0.683 AC: 3289 AN: 4814

European-Finnish (FIN) AF: 0.623 AC: 6566 AN: 10544

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35457 AN: 67956

Other (OTH) AF: 0.609 AC: 1286 AN: 2112

Alfa AF: 0.550 Hom.: 70987

Bravo AF: 0.606

Asia WGS AF: 0.759 AC: 2641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.98
DANN	Benign	0.45
PhyloP100		-0.13
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: rs1835538; hg19: chr3-30655481;