Genetic Variant NM_003247.5:c.2152-87C>G (chr6-169229766-G-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.2152-87C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,083,938 control chromosomes in the GnomAD database, including 27,060 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 0.26 ( 5899 hom., cov: 33)

Exomes 𝑓: 0.20 ( 21161 hom. )

Consequence

THBS2
NM_003247.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.739

Publications

5 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5 link	c.2152-87C>G		intron_variant	Intron 13 of 21	ENST00000617924.6	NP_003238.2	P35442

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6 link	c.2152-87C>G		intron_variant	Intron 13 of 21	1	NM_003247.5	ENSP00000482784.1		P35442

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39846

AN:

151892

Hom.:

5883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.204

AC:

190355

AN:

931928

Hom.:

21161

AF XY:

0.203

AC XY:

97223

AN XY:

478908

show subpopulations

African (AFR)

AF:

0.401

AC:

9254

AN:

23060

American (AMR)

AF:

0.327

AC:

13094

AN:

40030

Ashkenazi Jewish (ASJ)

AF:

0.166

AC:

3455

AN:

20804

East Asian (EAS)

AF:

0.338

AC:

12391

AN:

36634

South Asian (SAS)

AF:

0.215

AC:

15167

AN:

70390

European-Finnish (FIN)

AF:

0.242

AC:

10279

AN:

42464

Middle Eastern (MID)

AF:

0.225

AC:

1053

AN:

4690

European-Non Finnish (NFE)

AF:

0.179

AC:

116307

AN:

651042

Other (OTH)

AF:

0.219

AC:

9355

AN:

42814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

7204

14409

21613

28818

36022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3356

6712

10068

13424

16780

<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:

0.263

AC:

39918

AN:

152010

Hom.:

5899

Cov.:

AF XY:

0.264

AC XY:

19622

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.394

AC:

16333

AN:

41424

American (AMR)

AF:

0.269

AC:

4108

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

580

AN:

3462

East Asian (EAS)

AF:

0.357

AC:

1843

AN:

5158

South Asian (SAS)

AF:

0.226

AC:

1089

AN:

4812

European-Finnish (FIN)

AF:

0.239

AC:

2529

AN:

10560

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12568

AN:

67988

Other (OTH)

AF:

0.259

AC:

547

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1444

2887

4331

5774

7218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.106

Hom.:

153

Bravo

AF:

0.274

Asia WGS

AF:

0.325

AC:

1129

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.90

(source)

DANN

Benign

0.46

PhyloP100

-0.74

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