Variant 6-169222395-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_003247.5(THBS2):c.3075C>T(p.Ala1025=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,613,452 control chromosomes in the GnomAD database, including 31,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.21 ( 3550 hom., cov: 33)

Exomes 𝑓: 0.19 ( 28350 hom. )

Consequence

THBS2
NM_003247.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -5.67

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 6-169222395-G-A is Benign according to our data. Variant chr6-169222395-G-A is described in ClinVar as [Benign]. Clinvar id is 3059272.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-5.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS2	NM_003247.5 linkuse as main transcript	c.3075C>T	p.Ala1025=	synonymous_variant	19/22	ENST00000617924.6
THBS2-AS1	NR_134621.1 linkuse as main transcript	n.681+7908G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS2	ENST00000617924.6 linkuse as main transcript	c.3075C>T	p.Ala1025=	synonymous_variant	19/22	1	NM_003247.5	P4
THBS2-AS1	ENST00000660724.1 linkuse as main transcript	n.639+7908G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32338

AN:

151972

Hom.:

3535

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.197

Gnomad OTH

AF:

0.203

GnomAD3 exomes

AF:

0.204

AC:

51303

AN:

251272

Hom.:

5294

AF XY:

0.202

AC XY:

27486

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.222

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.155

Gnomad SAS exome

AF:

0.201

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.196

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.195

AC:

284745

AN:

1461362

Hom.:

28350

Cov.:

AF XY:

0.195

AC XY:

141477

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.254

Gnomad4 AMR exome

AF:

0.219

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.240

Gnomad4 NFE exome

AF:

0.191

Gnomad4 OTH exome

AF:

0.198

GnomAD4 genome

AF:

0.213

AC:

32386

AN:

152090

Hom.:

3550

Cov.:

AF XY:

0.214

AC XY:

15907

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.203

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.151

Gnomad4 SAS

AF:

0.204

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.197

Gnomad4 OTH

AF:

0.204

Alfa

AF:

0.202

Hom.:

1642

Bravo

AF:

0.214

Asia WGS

AF:

0.222

AC:

769

AN:

3478

EpiCase

AF:

0.192

EpiControl

AF:

0.189

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

THBS2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 02, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.091

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over