Variant 6-169221505-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_003247.5(THBS2):c.3296C>T(p.Pro1099Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,613,928 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0084 ( 3 hom., cov: 33)

Exomes 𝑓: 0.011 ( 118 hom. )

Consequence

THBS2
NM_003247.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.31

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 made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, THBS2

BP4

Computational evidence support a benign effect (MetaRNN=0.014176279).

BP6

Variant 6-169221505-G-A is Benign according to our data. Variant chr6-169221505-G-A is described in ClinVar as [Benign]. Clinvar id is 771721.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 1273 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS2	NM_003247.5 linkuse as main transcript	c.3296C>T	p.Pro1099Leu	missense_variant	20/22	ENST00000617924.6
THBS2-AS1	NR_134621.1 linkuse as main transcript	n.681+7018G>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.3296C>T	p.Pro1099Leu	missense_variant	20/22	1	NM_003247.5	P4
THBS2-AS1	ENST00000660724.1 linkuse as main transcript	n.639+7018G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00837

AC:

1273

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00675

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0193

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00898

AC:

2259

AN:

251424

Hom.:

AF XY:

0.00915

AC XY:

1244

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00428

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00323

Gnomad FIN exome

AF:

0.0198

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.0112

AC:

16401

AN:

1461692

Hom.:

118

Cov.:

AF XY:

0.0110

AC XY:

8018

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00485

Gnomad4 ASJ exome

AF:

0.00421

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00345

Gnomad4 FIN exome

AF:

0.0220

Gnomad4 NFE exome

AF:

0.0126

Gnomad4 OTH exome

AF:

0.00907

GnomAD4 genome

AF:

0.00836

AC:

1273

AN:

152236

Hom.:

Cov.:

AF XY:

0.00806

AC XY:

600

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00674

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0193

Gnomad4 NFE

AF:

0.0125

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.00753

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.00952

AC:

1156

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0117

EpiControl

AF:

0.0107

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.010

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.72

D;.;D

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.96

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Pathogenic

0.94

MutationAssessor

Uncertain

2.8

M;.;M

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-8.4

D;.;.

REVEL

Pathogenic

0.75

Sift

Uncertain

0.0060

D;.;.

Sift4G

Pathogenic

0.0010

D;.;D

Polyphen

1.0

D;.;D

Vest4

0.94

MVP

0.95

MPC

1.4

ClinPred

0.065

GERP RS

4.9

Varity_R

0.45

gMVP

0.68

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

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