Genetic Variant NM_003247.5:c.2152-136C>G (chr6-169229815-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.2152-136C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 641,872 control chromosomes in the GnomAD database, including 118,137 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 0.65 ( 33210 hom., cov: 32)

Exomes 𝑓: 0.58 ( 84927 hom. )

Consequence

THBS2
NM_003247.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.19

Publications

12 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:

Genome browser will be placed here

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=-1.04).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5 link	c.2152-136C>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.2152-136C>G		intron_variant	Intron 13 of 21	1	NM_003247.5	ENSP00000482784.1		P35442

Frequencies

GnomAD3 genomes

AF:

0.650

AC:

98795

AN:

151970

Hom.:

33145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.829

Gnomad AMI

AF:

0.568

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.673

Gnomad EAS

AF:

0.585

Gnomad SAS

AF:

0.600

Gnomad FIN

AF:

0.511

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.570

Gnomad OTH

AF:

0.650

GnomAD4 exome

AF:

0.583

AC:

285575

AN:

489784

Hom.:

84927

AF XY:

0.583

AC XY:

149327

AN XY:

256126

show subpopulations

African (AFR)

AF:

0.838

AC:

11196

AN:

13366

American (AMR)

AF:

0.657

AC:

13867

AN:

21116

Ashkenazi Jewish (ASJ)

AF:

0.669

AC:

9289

AN:

13894

East Asian (EAS)

AF:

0.549

AC:

16915

AN:

30832

South Asian (SAS)

AF:

0.600

AC:

26311

AN:

43838

European-Finnish (FIN)

AF:

0.525

AC:

15853

AN:

30206

Middle Eastern (MID)

AF:

0.664

AC:

2340

AN:

3522

European-Non Finnish (NFE)

AF:

0.566

AC:

173114

AN:

305924

Other (OTH)

AF:

0.616

AC:

16690

AN:

27086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

5538

11075

16613

22150

27688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1760

3520

5280

7040

8800

<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:

0.650

AC:

98922

AN:

152088

Hom.:

33210

Cov.:

AF XY:

0.648

AC XY:

48203

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.829

AC:

34420

AN:

41512

American (AMR)

AF:

0.655

AC:

10017

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.673

AC:

2333

AN:

3468

East Asian (EAS)

AF:

0.585

AC:

3020

AN:

5160

South Asian (SAS)

AF:

0.602

AC:

2893

AN:

4808

European-Finnish (FIN)

AF:

0.511

AC:

5398

AN:

10562

Middle Eastern (MID)

AF:

0.693

AC:

201

AN:

290

European-Non Finnish (NFE)

AF:

0.570

AC:

38746

AN:

67974

Other (OTH)

AF:

0.654

AC:

1377

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1686

3373

5059

6746

8432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.614

Hom.:

3601

Bravo

AF:

0.669

Asia WGS

AF:

0.659

AC:

2293

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.11

(source)

DANN

Benign

0.31

PhyloP100

-4.2

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over