6-169243590-C-T

Position:

• chr6-169243590-C-T

Variant summary

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

The NM_003247.5(THBS2):​c.695-1632G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,126 control chromosomes in the GnomAD database, including 15,509 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 0.43 (15509 hom., cov: 33)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THBS2	NM_003247.5	c.695-1632G>A		intron_variant		ENST00000617924.6	NP_003238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6	c.695-1632G>A		intron_variant		1	NM_003247.5	ENSP00000482784.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65580 AN: 152008 Hom.: 15502 Cov.: 33

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.431 AC: 65626 AN: 152126 Hom.: 15509 Cov.: 33 AF XY: 0.431 AC XY: 32066 AN XY: 74378

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.396

Alfa AF: 0.350 Hom.: 15672

Bravo AF: 0.452

Asia WGS AF: 0.533 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.54

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: rs9379341; hg19: chr6-169643685;