rs2043136

Positions:

• chr3-30678812-G-A
• chr3-30678812-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003242.6(TGFBR2):​c.1396+4566G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,034 control chromosomes in the GnomAD database, including 40,774 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 0.73 (40774 hom., cov: 31)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.1396+4566G>A		intron_variant		ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.1396+4566G>A		intron_variant		1	NM_003242.6	ENSP00000295754	P1
TGFBR2	ENST00000359013.4	c.1471+4566G>A		intron_variant		1		ENSP00000351905
TGFBR2	ENST00000672866.1	n.2992+4566G>A		intron_variant, non_coding_transcript_variant
TGFBR2	ENST00000673203.1	n.274+4566G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111035 AN: 151916 Hom.: 40749 Cov.: 31

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.731 AC: 111114 AN: 152034 Hom.: 40774 Cov.: 31 AF XY: 0.724 AC XY: 53842 AN XY: 74320

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.741

Alfa AF: 0.745 Hom.: 84560

Bravo AF: 0.745

Asia WGS AF: 0.592 AC: 2060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.14

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: rs2043136; hg19: chr3-30720304;