3-30691909-TTATATATATA-TTATATATATATA

Position:

• chr3-30691909-TTATATATATA-TTATATATATATA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003242.6(TGFBR2):​c.*328_*329dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.075 (1092 hom., cov: 0)
  • Exomes 𝑓: 0.012 (7 hom.)
• Consequence: TGFBR2 NM_003242.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.163

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 -10 ACMG points.

• BP6: Variant 3-30691909-T-TTA is Benign according to our data. Variant chr3-30691909-T-TTA is described in ClinVar as [Benign]. Clinvar id is 1231162.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR2	NM_003242.6	c.*328_*329dup		3_prime_UTR_variant	7/7	ENST00000295754.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR2	ENST00000295754.10	c.*328_*329dup		3_prime_UTR_variant	7/7	1	NM_003242.6	P1

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11064 AN: 147250 Hom.: 1093 Cov.: 0

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00222

Gnomad AMR AF: 0.0411

Gnomad ASJ AF: 0.0152

Gnomad EAS AF: 0.00668

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.00621

Gnomad MID AF: 0.0621

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.0582

GnomAD4 exome AF: 0.0116 AC: 1151 AN: 98988 Hom.: 7 Cov.: 0 AF XY: 0.0105 AC XY: 517 AN XY: 49106

Gnomad4 AFR exome AF: 0.0931

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.00910

Gnomad4 EAS exome AF: 0.00886

Gnomad4 SAS exome AF: 0.00133

Gnomad4 FIN exome AF: 0.00247

Gnomad4 NFE exome AF: 0.00732

Gnomad4 OTH exome AF: 0.0187

GnomAD4 genome AF: 0.0752 AC: 11071 AN: 147286 Hom.: 1092 Cov.: 0 AF XY: 0.0725 AC XY: 5200 AN XY: 71712

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.0409

Gnomad4 ASJ AF: 0.0152

Gnomad4 EAS AF: 0.00670

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.00621

Gnomad4 NFE AF: 0.0113

Gnomad4 OTH AF: 0.0579

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 25, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4016180; hg19: chr3-30733401;