3-30672350-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003242.6(TGFBR2):c.1167C>T(p.Asn389Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,613,836 control chromosomes in the GnomAD database, including 3,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 365 hom., cov: 32)

Exomes 𝑓: 0.030 ( 2760 hom. )

Consequence

TGFBR2
NM_003242.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -3.87

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 3-30672350-C-T is Benign according to our data. Variant chr3-30672350-C-T is described in ClinVar as [Benign]. Clinvar id is 44652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-30672350-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.87 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR2	NM_003242.6 link	c.1167C>T	p.Asn389Asn	synonymous_variant	Exon 4 of 7	ENST00000295754.10	NP_003233.4	P37173-1A3QNQ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TGFBR2	ENST00000295754.10 link	c.1167C>T	p.Asn389Asn	synonymous_variant	Exon 4 of 7	1	NM_003242.6	ENSP00000295754.5	P37173-1
TGFBR2	ENST00000359013.4 link	c.1242C>T	p.Asn414Asn	synonymous_variant	Exon 5 of 8	1		ENSP00000351905.4	P37173-2
TGFBR2	ENST00000672866.1 link	n.2763C>T		non_coding_transcript_exon_variant	Exon 4 of 7

Frequencies

GnomAD3 genomes

AF:

0.0361

AC:

5499

AN:

152164

Hom.:

365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0332

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.0533

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0480

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0278

GnomAD3 exomes

AF:

0.0550

AC:

13784

AN:

250540

Hom.:

1253

AF XY:

0.0568

AC XY:

7692

AN XY:

135358

show subpopulations

Gnomad AFR exome

AF:

0.0330

Gnomad AMR exome

AF:

0.0167

Gnomad ASJ exome

AF:

0.0447

Gnomad EAS exome

AF:

0.305

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.0460

Gnomad NFE exome

AF:

0.0145

Gnomad OTH exome

AF:

0.0408

GnomAD4 exome

AF:

0.0297

AC:

43365

AN:

1461554

Hom.:

2760

Cov.:

AF XY:

0.0321

AC XY:

23361

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.0346

Gnomad4 AMR exome

AF:

0.0153

Gnomad4 ASJ exome

AF:

0.0428

Gnomad4 EAS exome

AF:

0.281

Gnomad4 SAS exome

AF:

0.117

Gnomad4 FIN exome

AF:

0.0450

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.0420

GnomAD4 genome

AF:

0.0361

AC:

5500

AN:

152282

Hom.:

365

Cov.:

AF XY:

0.0410

AC XY:

3055

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0333

Gnomad4 AMR

AF:

0.0127

Gnomad4 ASJ

AF:

0.0533

Gnomad4 EAS

AF:

0.303

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.0480

Gnomad4 NFE

AF:

0.0141

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0177

Hom.:

Bravo

AF:

0.0319

Asia WGS

AF:

0.191

AC:

662

AN:

3478

EpiCase

AF:

0.0123

EpiControl

AF:

0.0120

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 27, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Aug 29, 2007

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 25, 2019

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:2

Mar 15, 2018

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Loeys-Dietz syndrome 2

Benign:2

Oct 01, 2024

All of Us Research Program, National Institutes of Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Marfan syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Loeys-Dietz syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cardiovascular phenotype

Benign:1

Feb 19, 2015

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance -

Thoracic aortic aneurysm

Benign:1

Sep 23, 2022

Cohesion Phenomics

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.19

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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