3-30691909-TTATATATATA-TTATATATATATATATA

Position:

• chr3-30691909-TTATATATATA-TTATATATATATATATA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003242.6(TGFBR2):​c.*324_*329dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: TGFBR2 NM_003242.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.*324_*329dup		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.*324_*329dup		3_prime_UTR_variant	7/7	1	NM_003242.6	ENSP00000295754	P1

Frequencies

GnomAD3 genomes AF: 0.000136 AC: 20 AN: 147324 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000271

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000999 AC: 1 AN: 100116 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 49628

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000190

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000136 AC: 20 AN: 147360 Hom.: 0 Cov.: 0 AF XY: 0.0000558 AC XY: 4 AN XY: 71738

Gnomad4 AFR AF: 0.000326

Gnomad4 AMR AF: 0.000271

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000149

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;