Genetic Variant THBS2:c.*191T>G (chr6-169217631-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003247.5(THBS2):c.*191T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 545,236 control chromosomes in the GnomAD database, including 13,710 homozygotes. 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: 𝑓 0.22 ( 3783 hom., cov: 33)

Exomes 𝑓: 0.22 ( 9927 hom. )

Consequence

THBS2
NM_003247.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.401

Publications

33 publications found

Variant links:

Genes affected

THBS2 (HGNC:11786): (thrombospondin 2) The protein encoded by this gene belongs to the thrombospondin family. It is a disulfide-linked homotrimeric glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein has been shown to function as a potent inhibitor of tumor growth and angiogenesis. Studies of the mouse counterpart suggest that this protein may modulate the cell surface properties of mesenchymal cells and be involved in cell adhesion and migration. [provided by RefSeq, Jul 2008]

THBS2 links:

THBS2-AS1 (HGNC:56059): (THBS2 antisense RNA 1)

THBS2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5 link	c.*191T>G		3_prime_UTR_variant	Exon 22 of 22	ENST00000617924.6	NP_003238.2	P35442

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6 link	c.*191T>G		3_prime_UTR_variant	Exon 22 of 22	1	NM_003247.5	ENSP00000482784.1		P35442

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32792

AN:

151980

Hom.:

3780

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.0988

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.230

GnomAD4 exome

AF:

0.215

AC:

84596

AN:

393138

Hom.:

9927

Cov.:

AF XY:

0.212

AC XY:

43210

AN XY:

204294

show subpopulations

African (AFR)

AF:

0.213

AC:

2225

AN:

10444

American (AMR)

AF:

0.156

AC:

1826

AN:

11688

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

3204

AN:

11954

East Asian (EAS)

AF:

0.0949

AC:

2579

AN:

27180

South Asian (SAS)

AF:

0.109

AC:

2801

AN:

25688

European-Finnish (FIN)

AF:

0.163

AC:

6552

AN:

40164

Middle Eastern (MID)

AF:

0.244

AC:

434

AN:

1776

European-Non Finnish (NFE)

AF:

0.247

AC:

59719

AN:

241590

Other (OTH)

AF:

0.232

AC:

5256

AN:

22654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3191

6383

9574

12766

15957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.216

AC:

32811

AN:

152098

Hom.:

3783

Cov.:

AF XY:

0.211

AC XY:

15660

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.211

AC:

8758

AN:

41474

American (AMR)

AF:

0.180

AC:

2743

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

991

AN:

3472

East Asian (EAS)

AF:

0.0989

AC:

511

AN:

5168

South Asian (SAS)

AF:

0.111

AC:

534

AN:

4828

European-Finnish (FIN)

AF:

0.167

AC:

1770

AN:

10586

Middle Eastern (MID)

AF:

0.240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.246

AC:

16719

AN:

67996

Other (OTH)

AF:

0.229

AC:

482

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1309

2618

3926

5235

6544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

344

688

1032

1376

1720

<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:

0.238

Hom.:

7335

Bravo

AF:

0.219

Asia WGS

AF:

0.109

AC:

383

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.6

(source)

DANN

Benign

0.48

PhyloP100

0.40

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over