rs146497045

Positions:

• chr3-30650400-A-C
• chr3-30650400-A-G
• chr3-30650400-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003242.6(TGFBR2):​c.394A>C​(p.Thr132Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TGFBR2 NM_003242.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.908

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22138691).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.394A>C	p.Thr132Pro	missense_variant	3/7	ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.394A>C	p.Thr132Pro	missense_variant	3/7	1	NM_003242.6	ENSP00000295754	P1
TGFBR2	ENST00000359013.4	c.469A>C	p.Thr157Pro	missense_variant	4/8	1		ENSP00000351905
TGFBR2	ENST00000672866.1	n.1990A>C		non_coding_transcript_exon_variant	3/7
TGFBR2	ENST00000673250.1	n.518A>C		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.088
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	0.56	D;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.30	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0	B;.
Vest4		0.33
MutPred		0.51		Gain of catalytic residue at T132 (P = 0.0025);.;
MVP		0.98
MPC		0.70
ClinPred		0.23	T
GERP RS		6.0
Varity_R		0.49
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-30691892;