6-169222283-C-T

Variant names:

• chr6-169222283-C-T
• rs769806537
• NM_003247.5:c.3187G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003247.5(THBS2):​c.3187G>A​(p.Val1063Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,613,162 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: THBS2 NM_003247.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.49
• Publications: 1 publications found

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-AS1 (HGNC:56059): (THBS2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 5 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS2	NM_003247.5	MANE Select	c.3187G>A	p.Val1063Met	missense	Exon 19 of 22	NP_003238.2
	THBS2	NM_001381939.1		c.3013G>A	p.Val1005Met	missense	Exon 18 of 21	NP_001368868.1	A0A7I2V585
	THBS2	NM_001381942.1		c.2956G>A	p.Val986Met	missense	Exon 19 of 22	NP_001368871.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS2	ENST00000617924.6	TSL:1 MANE Select	c.3187G>A	p.Val1063Met	missense	Exon 19 of 22	ENSP00000482784.1	P35442
	THBS2	ENST00000366787.7	TSL:1	c.3187G>A	p.Val1063Met	missense	Exon 20 of 23	ENSP00000355751.3	P35442
	THBS2	ENST00000649844.1		c.3202G>A	p.Val1068Met	missense	Exon 19 of 22	ENSP00000497834.1	A0A3B3ITK0

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000280 AC: 7 AN: 250198 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000349 AC: 51 AN: 1460984 Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 28 AN XY: 726794

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000405 AC: 45 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60380

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152178 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.27	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Benign	1.9	L
PhyloP100		4.5
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.1	N
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.67
MVP		0.96
MPC		1.4
ClinPred		0.40	T
GERP RS		4.3
Varity_R		0.28
gMVP		0.61
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs769806537; hg19: chr6-169622378; COSMIC: COSV104680262;