rs13192849

Positions:

• chr6-169240637-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003247.5(THBS2):​c.892-45T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 1,587,562 control chromosomes in the GnomAD database, including 7,106 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 0.14 (2716 hom., cov: 33)
  • Exomes 𝑓: 0.054 (4390 hom.)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THBS2	NM_003247.5	c.892-45T>G		intron_variant		ENST00000617924.6	NP_003238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6	c.892-45T>G		intron_variant		1	NM_003247.5	ENSP00000482784	P4
THBS2-AS1	ENST00000660724.1	n.2052A>C		non_coding_transcript_exon_variant	3/4

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20722 AN: 152130 Hom.: 2712 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.0406

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.0540

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0398

Gnomad OTH AF: 0.111

GnomAD3 exomes AF: 0.0841 AC: 20253 AN: 240894 Hom.: 1660 AF XY: 0.0771 AC XY: 10055 AN XY: 130344

Gnomad AFR exome AF: 0.356

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.0340

Gnomad EAS exome AF: 0.193

Gnomad SAS exome AF: 0.0565

Gnomad FIN exome AF: 0.0577

Gnomad NFE exome AF: 0.0389

Gnomad OTH exome AF: 0.0714

GnomAD4 exome AF: 0.0536 AC: 76921 AN: 1435314 Hom.: 4390 Cov.: 29 AF XY: 0.0526 AC XY: 37388 AN XY: 710176

Gnomad4 AFR exome AF: 0.360

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.0360

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.0531

Gnomad4 FIN exome AF: 0.0561

Gnomad4 NFE exome AF: 0.0371

Gnomad4 OTH exome AF: 0.0713

GnomAD4 genome AF: 0.136 AC: 20758 AN: 152248 Hom.: 2716 Cov.: 33 AF XY: 0.134 AC XY: 10011 AN XY: 74446

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.0899

Gnomad4 ASJ AF: 0.0406

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.0536

Gnomad4 FIN AF: 0.0620

Gnomad4 NFE AF: 0.0398

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0829 Hom.: 247

Bravo AF: 0.150

Asia WGS AF: 0.124 AC: 429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.10
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs13192849; hg19: chr6-169640732; COSMIC: COSV64677758; COSMIC: COSV64677758;