Genetic Variant THBS2:c.1301-78G>A (chr6-169237424-C-T) – 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.1301-78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,557,268 control chromosomes in the GnomAD database, including 257,987 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 0.61 ( 29309 hom., cov: 34)

Exomes 𝑓: 0.57 ( 228678 hom. )

Consequence

THBS2
NM_003247.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09

Publications

8 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 (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5 link	c.1301-78G>A		intron_variant	Intron 8 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.1301-78G>A		intron_variant	Intron 8 of 21	1	NM_003247.5	ENSP00000482784.1		P35442

Frequencies

GnomAD3 genomes

AF:

0.613

AC:

93179

AN:

152020

Hom.:

29259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.691

Gnomad AMI

AF:

0.734

Gnomad AMR

AF:

0.657

Gnomad ASJ

AF:

0.596

Gnomad EAS

AF:

0.898

Gnomad SAS

AF:

0.595

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.554

Gnomad OTH

AF:

0.632

GnomAD4 exome

AF:

0.566

AC:

794860

AN:

1405130

Hom.:

228678

Cov.:

AF XY:

0.566

AC XY:

396237

AN XY:

700422

show subpopulations

African (AFR)

AF:

0.692

AC:

22138

AN:

31978

American (AMR)

AF:

0.707

AC:

29851

AN:

42196

Ashkenazi Jewish (ASJ)

AF:

0.568

AC:

14555

AN:

25612

East Asian (EAS)

AF:

0.890

AC:

34714

AN:

39010

South Asian (SAS)

AF:

0.593

AC:

50079

AN:

84500

European-Finnish (FIN)

AF:

0.490

AC:

22852

AN:

46664

Middle Eastern (MID)

AF:

0.576

AC:

3180

AN:

5518

European-Non Finnish (NFE)

AF:

0.544

AC:

583089

AN:

1071206

Other (OTH)

AF:

0.589

AC:

34402

AN:

58446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

17293

34586

51878

69171

86464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16500

33000

49500

66000

82500

<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:

0.613

AC:

93285

AN:

152138

Hom.:

29309

Cov.:

AF XY:

0.611

AC XY:

45440

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.691

AC:

28685

AN:

41498

American (AMR)

AF:

0.658

AC:

10055

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.596

AC:

2069

AN:

3470

East Asian (EAS)

AF:

0.898

AC:

4629

AN:

5152

South Asian (SAS)

AF:

0.597

AC:

2878

AN:

4822

European-Finnish (FIN)

AF:

0.487

AC:

5167

AN:

10604

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.554

AC:

37631

AN:

67984

Other (OTH)

AF:

0.633

AC:

1339

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1859

3717

5576

7434

9293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

768

1536

2304

3072

3840

<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:

0.584

Hom.:

6464

Bravo

AF:

0.633

Asia WGS

AF:

0.753

AC:

2615

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

0.037

(source)

DANN

Benign

0.43

PhyloP100

-1.1

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