rs11758161

Variant names:

• chr6-169251249-C-T
• rs11758161
• NM_003247.5:c.-22-443G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003247.5(THBS2):​c.-22-443G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,106 control chromosomes in the GnomAD database, including 1,870 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 0.15 (1870 hom., cov: 33)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 6 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 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, classic-like, 3

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5	c.-22-443G>A		intron_variant	Intron 1 of 21	ENST00000617924.6	NP_003238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6	c.-22-443G>A		intron_variant	Intron 1 of 21	1	NM_003247.5	ENSP00000482784.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22845 AN: 151988 Hom.: 1863 Cov.: 33

Gnomad AFR AF: 0.0813

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.150 AC: 22872 AN: 152106 Hom.: 1870 Cov.: 33 AF XY: 0.152 AC XY: 11333 AN XY: 74344

African (AFR) AF: 0.0812 AC: 3368 AN: 41500

American (AMR) AF: 0.200 AC: 3051 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3470

East Asian (EAS) AF: 0.226 AC: 1170 AN: 5180

South Asian (SAS) AF: 0.198 AC: 955 AN: 4816

European-Finnish (FIN) AF: 0.177 AC: 1861 AN: 10534

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11397 AN: 68010

Other (OTH) AF: 0.173 AC: 366 AN: 2110

Alfa AF: 0.162 Hom.: 1090

Bravo AF: 0.150

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.78
PhyloP100		-0.51
PromoterAI		-0.026	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs11758161; hg19: chr6-169651344;