dbSNP rs6422747: THBS2:c.2152-9C>T (chr6-169229688-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003247.5(THBS2):c.2152-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,606,948 control chromosomes in the GnomAD database, including 286,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.67 ( 36273 hom., cov: 33)

Exomes 𝑓: 0.58 ( 250050 hom. )

Consequence

THBS2
NM_003247.5 intron

Scores

Splicing: ADA: 0.00002677

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.431

Publications

17 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 6-169229688-G-A is Benign according to our data. Variant chr6-169229688-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059455.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003247.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
THBS2	NM_003247.5	MANE Select	c.2152-9C>T	intron	N/A	NP_003238.2
THBS2	NM_001381939.1		c.1978-9C>T	intron	N/A	NP_001368868.1	A0A7I2V585
THBS2	NM_001381942.1		c.1921-9C>T	intron	N/A	NP_001368871.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
THBS2	ENST00000617924.6	TSL:1 MANE Select	c.2152-9C>T	intron	N/A	ENSP00000482784.1	P35442
THBS2	ENST00000366787.7	TSL:1	c.2152-9C>T	intron	N/A	ENSP00000355751.3	P35442
THBS2	ENST00000649844.1		c.2167-9C>T	intron	N/A	ENSP00000497834.1	A0A3B3ITK0

Frequencies

GnomAD3 genomes

AF:

0.673

AC:

102348

AN:

151970

Hom.:

36203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.910

Gnomad AMI

AF:

0.567

Gnomad AMR

AF:

0.662

Gnomad ASJ

AF:

0.672

Gnomad EAS

AF:

0.585

Gnomad SAS

AF:

0.601

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.571

Gnomad OTH

AF:

0.665

GnomAD2 exomes

AF:

0.612

AC:

153483

AN:

250848

AF XY:

0.604

show subpopulations

Gnomad AFR exome

AF:

0.917

Gnomad AMR exome

AF:

0.661

Gnomad ASJ exome

AF:

0.665

Gnomad EAS exome

AF:

0.593

Gnomad FIN exome

AF:

0.520

Gnomad NFE exome

AF:

0.570

Gnomad OTH exome

AF:

0.617

GnomAD4 exome

AF:

0.583

AC:

847636

AN:

1454860

Hom.:

250050

Cov.:

AF XY:

0.582

AC XY:

421732

AN XY:

724158

show subpopulations

African (AFR)

AF:

0.925

AC:

30870

AN:

33360

American (AMR)

AF:

0.660

AC:

29448

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

17406

AN:

26078

East Asian (EAS)

AF:

0.558

AC:

22129

AN:

39652

South Asian (SAS)

AF:

0.603

AC:

51825

AN:

86014

European-Finnish (FIN)

AF:

0.523

AC:

27898

AN:

53296

Middle Eastern (MID)

AF:

0.666

AC:

3829

AN:

5748

European-Non Finnish (NFE)

AF:

0.567

AC:

627111

AN:

1105936

Other (OTH)

AF:

0.617

AC:

37120

AN:

60130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

17176

34352

51528

68704

85880

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17576

35152

52728

70304

87880

<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:

0.674

AC:

102481

AN:

152088

Hom.:

36273

Cov.:

AF XY:

0.670

AC XY:

49827

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.910

AC:

37814

AN:

41544

American (AMR)

AF:

0.662

AC:

10118

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.672

AC:

2333

AN:

3472

East Asian (EAS)

AF:

0.585

AC:

3012

AN:

5148

South Asian (SAS)

AF:

0.602

AC:

2897

AN:

4812

European-Finnish (FIN)

AF:

0.512

AC:

5405

AN:

10558

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.571

AC:

38774

AN:

67960

Other (OTH)

AF:

0.669

AC:

1410

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1574

3149

4723

6298

7872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

792

1584

2376

3168

3960

<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:

0.629

Hom.:

13954

Bravo

AF:

0.695

Asia WGS

AF:

0.665

AC:

2313

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

THBS2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.048

(source)

DANN

Benign

0.77

PhyloP100

-0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000027

dbscSNV1_RF

Benign

0.0060

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over