rs1697919506

Variant names:

• chr3-30606496-C-A
• rs1697919506
• XM_047449400.1:c.429G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-30606496-C-A
• chr3-30606496-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001407129.1(TGFBR2):​c.-109C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 96,256 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: TGFBR2 NM_001407129.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 0 publications found

Genes affected

LOC105377015 (HGNC:):

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):

• Loeys-Dietz syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: Unknown, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Loeys-Dietz syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001407129.1. 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_001407129.1		c.-109C>A		5_prime_UTR	Exon 1 of 8	NP_001394058.1
	TGFBR2	NM_001407132.1		c.-109C>A		5_prime_UTR	Exon 1 of 7	NP_001394061.1	A0AAQ5BI06
	TGFBR2	NM_003242.6	MANE Select	c.-388C>A		upstream_gene	N/A	NP_003233.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR2	ENST00000714391.1		c.-106C>A		5_prime_UTR	Exon 1 of 8	ENSP00000519658.1	A0AAQ5BI03
	TGFBR2	ENST00000714389.1		c.-104C>A		5_prime_UTR	Exon 1 of 7	ENSP00000519656.1	A0AAQ5BI06
	TGFBR2	ENST00000714390.1		c.-109C>A		5_prime_UTR	Exon 1 of 7	ENSP00000519657.1	A0AAQ5BI06

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000104 AC: 1 AN: 96256 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 45256

African (AFR) AF: 0.00 AC: 0 AN: 4400

American (AMR) AF: 0.00 AC: 0 AN: 2810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5494

East Asian (EAS) AF: 0.00 AC: 0 AN: 12116

South Asian (SAS) AF: 0.00 AC: 0 AN: 836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 604

European-Non Finnish (NFE) AF: 0.0000167 AC: 1 AN: 59812

Other (OTH) AF: 0.00 AC: 0 AN: 7726

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.2
DANN	Benign	0.54
PhyloP100		0.075
PromoterAI		-0.18	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1697919506; hg19: chr3-30647988;