Genetic Variant THBS2:c.3511+46A>G (chr6-169220152-T-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.3511+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,592,622 control chromosomes in the GnomAD database, including 361,261 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 0.72 ( 39717 hom., cov: 31)

Exomes 𝑓: 0.67 ( 321544 hom. )

Consequence

THBS2
NM_003247.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0660

Publications

10 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=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5 link	c.3511+46A>G		intron_variant	Intron 21 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.3511+46A>G		intron_variant	Intron 21 of 21	1	NM_003247.5	ENSP00000482784.1		P35442

Frequencies

GnomAD3 genomes

AF:

0.716

AC:

108812

AN:

151892

Hom.:

39665

Cov.:

show subpopulations

Gnomad AFR

AF:

0.858

Gnomad AMI

AF:

0.710

Gnomad AMR

AF:

0.721

Gnomad ASJ

AF:

0.692

Gnomad EAS

AF:

0.479

Gnomad SAS

AF:

0.650

Gnomad FIN

AF:

0.628

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.667

Gnomad OTH

AF:

0.711

GnomAD2 exomes

AF:

0.669

AC:

158439

AN:

236844

AF XY:

0.665

show subpopulations

Gnomad AFR exome

AF:

0.857

Gnomad AMR exome

AF:

0.716

Gnomad ASJ exome

AF:

0.684

Gnomad EAS exome

AF:

0.498

Gnomad FIN exome

AF:

0.627

Gnomad NFE exome

AF:

0.666

Gnomad OTH exome

AF:

0.671

GnomAD4 exome

AF:

0.666

AC:

959320

AN:

1440612

Hom.:

321544

Cov.:

AF XY:

0.665

AC XY:

474899

AN XY:

714290

show subpopulations

African (AFR)

AF:

0.871

AC:

28698

AN:

32954

American (AMR)

AF:

0.714

AC:

30714

AN:

43004

Ashkenazi Jewish (ASJ)

AF:

0.681

AC:

16802

AN:

24688

East Asian (EAS)

AF:

0.470

AC:

18528

AN:

39446

South Asian (SAS)

AF:

0.655

AC:

54151

AN:

82660

European-Finnish (FIN)

AF:

0.627

AC:

32913

AN:

52474

Middle Eastern (MID)

AF:

0.795

AC:

4463

AN:

5614

European-Non Finnish (NFE)

AF:

0.666

AC:

732472

AN:

1100294

Other (OTH)

AF:

0.682

AC:

40579

AN:

59478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

16498

32996

49493

65991

82489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19200

38400

57600

76800

96000

<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:

0.717

AC:

108921

AN:

152010

Hom.:

39717

Cov.:

AF XY:

0.715

AC XY:

53103

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.858

AC:

35596

AN:

41494

American (AMR)

AF:

0.720

AC:

11011

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.692

AC:

2399

AN:

3468

East Asian (EAS)

AF:

0.478

AC:

2455

AN:

5134

South Asian (SAS)

AF:

0.651

AC:

3132

AN:

4808

European-Finnish (FIN)

AF:

0.628

AC:

6646

AN:

10578

Middle Eastern (MID)

AF:

0.801

AC:

234

AN:

292

European-Non Finnish (NFE)

AF:

0.667

AC:

45305

AN:

67930

Other (OTH)

AF:

0.709

AC:

1497

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1528

3056

4584

6112

7640

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

826

1652

2478

3304

4130

<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:

0.687

Hom.:

47867

Bravo

AF:

0.728

Asia WGS

AF:

0.595

AC:

2069

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.11

(source)

DANN

Benign

0.32

PhyloP100

-0.066

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