rs863223790

Variant names:

• chr1-218434154-G-C
• NM_003238.6:c.583G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-218434154-G-C
• chr1-218434154-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003238.6(TGFB2):​c.583G>C​(p.Glu195Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TGFB2 NM_003238.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.70

Genes affected

TGFB2 (HGNC:11768): (transforming growth factor beta 2) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGF-beta family members. Disruption of the TGF-beta/SMAD pathway has been implicated in a variety of human cancers. A chromosomal translocation that includes this gene is associated with Peters' anomaly, a congenital defect of the anterior chamber of the eye. Mutations in this gene may be associated with Loeys-Dietz syndrome. This gene encodes multiple isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34353173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFB2	NM_003238.6	c.583G>C	p.Glu195Gln	missense_variant	Exon 3 of 7	ENST00000366930.9	NP_003229.1
TGFB2	NM_001135599.4	c.667G>C	p.Glu223Gln	missense_variant	Exon 4 of 8		NP_001129071.1
TGFB2	NR_138148.2	n.1949G>C		non_coding_transcript_exon_variant	Exon 3 of 7
TGFB2	NR_138149.2	n.2033G>C		non_coding_transcript_exon_variant	Exon 4 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFB2	ENST00000366930.9	c.583G>C	p.Glu195Gln	missense_variant	Exon 3 of 7	1	NM_003238.6	ENSP00000355897.4
TGFB2	ENST00000366929.4	c.667G>C	p.Glu223Gln	missense_variant	Exon 4 of 8	1		ENSP00000355896.4
TGFB2	ENST00000479322.1	n.29G>C		non_coding_transcript_exon_variant	Exon 1 of 5	3
TGFB2	ENST00000488793.1	n.247G>C		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.62	N;N
REVEL	Benign	0.25
Sift	Benign	0.34	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.046	B;B
Vest4		0.58
MutPred		0.32		Gain of MoRF binding (P = 0.056);.;
MVP		0.85
MPC		1.4
ClinPred		0.88	D
GERP RS		5.9
Varity_R		0.12
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-218607496;