rs7382358

Positions:

• chr6-169246927-T-C

Variant summary

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

The NM_003247.5(THBS2):​c.610-646A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,168 control chromosomes in the GnomAD database, including 4,986 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 0.25 (4986 hom., cov: 33)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THBS2	NM_003247.5	c.610-646A>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.610-646A>G		intron_variant		1	NM_003247.5	ENSP00000482784.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38129 AN: 152052 Hom.: 4979 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.251 AC: 38157 AN: 152168 Hom.: 4986 Cov.: 33 AF XY: 0.254 AC XY: 18933 AN XY: 74398

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.273

Alfa AF: 0.274 Hom.: 6626

Bravo AF: 0.241

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.33

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

Other links and lift over

dbSNP: rs7382358; hg19: chr6-169647022;