rs2043138

chr3-30634525-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_003242.6(TGFBR2):c.95-10222G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 151,910 control chromosomes in the GnomAD database, including 36,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency: Genomes: 𝑓 0.68 (36275 hom., cov: 31)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-30634525-G-C is Benign according to our data. Variant chr3-30634525-G-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR2	NM_003242.6	c.95-10222G>C		intron_variant		ENST00000295754.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR2	ENST00000295754.10	c.95-10222G>C		intron_variant		1	NM_003242.6	P1
TGFBR2	ENST00000359013.4	c.170-10222G>C		intron_variant		1
TGFBR2	ENST00000672866.1	n.1690+1679G>C		intron_variant, non_coding_transcript_variant
TGFBR2	ENST00000673250.1	n.219-10222G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103611 AN: 151792 Hom.: 36235 Cov.: 31

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.683 AC: 103705 AN: 151910 Hom.: 36275 Cov.: 31 AF XY: 0.681 AC XY: 50559 AN XY: 74234

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.684

Alfa AF: 0.659 Hom.: 4185

Bravo AF: 0.693

Asia WGS AF: 0.691 AC: 2404 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	2.0
Dann	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs2043138; hg19: chr3-30676017;