rs17026332

Positions:

• chr3-30692434-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_003242.6(TGFBR2):​c.*835C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 231,860 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0098 (10 hom., cov: 32)
  • Exomes 𝑓: 0.011 (9 hom.)
• Consequence: TGFBR2 NM_003242.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.401

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-30692434-C-A is Benign according to our data. Variant chr3-30692434-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 344684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1485 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.*835C>A		3_prime_UTR_variant	7/7	ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.*835C>A		3_prime_UTR_variant	7/7	1	NM_003242.6	ENSP00000295754.5
TGFBR2	ENST00000359013.4	c.*835C>A		3_prime_UTR_variant	8/8	1		ENSP00000351905.4
TGFBR2	ENST00000672866.1	n.4135C>A		non_coding_transcript_exon_variant	7/7
TGFBR2	ENST00000673203.1	n.1417C>A		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.00976 AC: 1485 AN: 152166 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00263

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00801

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.0109 AC: 871 AN: 79576 Hom.: 9 Cov.: 0 AF XY: 0.0107 AC XY: 392 AN XY: 36606

Gnomad4 AFR exome AF: 0.00422

Gnomad4 AMR exome AF: 0.0126

Gnomad4 ASJ exome AF: 0.00238

Gnomad4 EAS exome AF: 0.000265

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0185

Gnomad4 NFE exome AF: 0.0149

Gnomad4 OTH exome AF: 0.0107

GnomAD4 genome AF: 0.00975 AC: 1485 AN: 152284 Hom.: 10 Cov.: 32 AF XY: 0.00906 AC XY: 675 AN XY: 74468

Gnomad4 AFR AF: 0.00262

Gnomad4 AMR AF: 0.0152

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00801

Gnomad4 NFE AF: 0.0145

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0119 Hom.: 4

Bravo AF: 0.0103

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 21, 2021	- -

Marfan syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Familial thoracic aortic aneurysm and aortic dissection Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Loeys-Dietz syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.68

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: rs17026332; hg19: chr3-30733926;