rs2005061

chr3-30649256-G-Achr3-30649256-G-Cchr3-30649256-G-T

Variant summary

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

The NM_003242.6(TGFBR2):c.264-1014G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,184 control chromosomes in the GnomAD database, including 1,716 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 0.14 (1716 hom., cov: 32)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR2	NM_003242.6	c.264-1014G>A		intron_variant		ENST00000295754.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR2	ENST00000295754.10	c.264-1014G>A		intron_variant		1	NM_003242.6	P1
TGFBR2	ENST00000359013.4	c.339-1014G>A		intron_variant		1
TGFBR2	ENST00000672866.1	n.1860-1014G>A		intron_variant, non_coding_transcript_variant
TGFBR2	ENST00000673250.1	n.388-1014G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21049 AN: 152066 Hom.: 1719 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.138 AC: 21058 AN: 152184 Hom.: 1716 Cov.: 32 AF XY: 0.140 AC XY: 10438 AN XY: 74400

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.140

Alfa AF: 0.140 Hom.: 1661

Bravo AF: 0.148

Asia WGS AF: 0.266 AC: 927 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	0.027
Dann	Benign	0.40

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: rs2005061; hg19: chr3-30690748;