dbSNP rs149215818: TGFB2:p.Glu38Glu (chr1-218346815-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_003238.6(TGFB2):c.114G>A(p.Glu38Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,614,168 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 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 18 hom. )

Consequence

TGFB2
NM_003238.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 2.90

Publications

4 publications found

Variant links:

COSMIC-nc: COSV100860542

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]

TGFB2 links:

TGFB2-AS1 (HGNC:50628): (TGFB2 antisense RNA 1 (head to head))

TGFB2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 1-218346815-G-A is Benign according to our data. Variant chr1-218346815-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 213834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.9 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00127 (193/152276) while in subpopulation SAS AF = 0.0133 (64/4824). AF 95% confidence interval is 0.0107. There are 1 homozygotes in GnomAd4. There are 102 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 193 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003238.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TGFB2	NM_003238.6	MANE Select	c.114G>A	p.Glu38Glu	synonymous	Exon 1 of 7	NP_003229.1	P61812-1
TGFB2	NM_001135599.4		c.114G>A	p.Glu38Glu	synonymous	Exon 1 of 8	NP_001129071.1	P61812-2
TGFB2	NR_138148.2		n.1480G>A		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TGFB2	ENST00000366930.9	TSL:1 MANE Select	c.114G>A	p.Glu38Glu	synonymous	Exon 1 of 7	ENSP00000355897.4	P61812-1
TGFB2	ENST00000366929.4	TSL:1	c.114G>A	p.Glu38Glu	synonymous	Exon 1 of 8	ENSP00000355896.4	P61812-2
TGFB2-AS1	ENST00000774588.1		n.238+814C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

194

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.00296

AC:

745

AN:

251466

AF XY:

0.00341

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00153

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00187

AC:

2730

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

1610

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.000827

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0114

AC:

297

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0127

AC:

1096

AN:

86258

European-Finnish (FIN)

AF:

0.000225

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00607

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000964

AC:

1072

AN:

1112010

Other (OTH)

AF:

0.00290

AC:

175

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

174

349

523

698

872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00127

AC:

193

AN:

152276

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41560

American (AMR)

AF:

0.000458

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.0133

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00116

AC:

AN:

68024

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00195

Hom.:

Bravo

AF:

0.000907

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00224

EpiControl

AF:

0.00207

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Loeys-Dietz syndrome 4 (4)

not specified (4)

not provided (3)

Familial thoracic aortic aneurysm and aortic dissection (2)

Connective tissue disorder (1)

Ehlers-Danlos syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

2.9

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over