Variant 3-30691329-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0520

Variant links:

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]

TGFBR2 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
TGFBR2	NM_003242.6 linkuse as main transcript	c.1525-91C>A		intron_variant		ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10 linkuse as main transcript	c.1525-91C>A		intron_variant		1	NM_003242.6	ENSP00000295754	P1	P37173-1

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34320

AN:

152050

Hom.:

4750

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.226

AC XY:

16828

AN XY:

74390

show subpopulations

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over