rs2276767

chr3-30691329-C-Achr3-30691329-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003242.6(TGFBR2):c.1525-91C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,427,188 control chromosomes in the GnomAD database, including 64,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4746 hom., cov: 32)
  • Exomes 𝑓: 0.29 (59394 hom.)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0520

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-30691329-C-A is Benign according to our data. Variant chr3-30691329-C-A is described in ClinVar as [Benign]. Clinvar id is 2687926.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR2	NM_003242.6	c.1525-91C>A		intron_variant		ENST00000295754.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR2	ENST00000295754.10	c.1525-91C>A		intron_variant		1	NM_003242.6	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34320 AN: 152050 Hom.: 4750 Cov.: 32

Gnomad AFR AF: 0.0936

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.294 AC: 375051 AN: 1275020 Hom.: 59394 AF XY: 0.290 AC XY: 185112 AN XY: 637688

Gnomad4 AFR exome AF: 0.0880

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.0870

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.225 AC: 34303 AN: 152168 Hom.: 4746 Cov.: 32 AF XY: 0.226 AC XY: 16828 AN XY: 74390

Gnomad4 AFR AF: 0.0934

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.0944

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.209

Alfa AF: 0.274 Hom.: 5753

Bravo AF: 0.202

Asia WGS AF: 0.131 AC: 456 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.6
Dann	Benign	0.61

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: rs2276767; hg19: chr3-30732821; COSMIC: COSV55443740;