rs6940420

Variant names:

• chr6-169231812-G-A
• rs6940420
• NM_003247.5:c.2151+168C>T

Variant summary

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

The NM_003247.5(THBS2):​c.2151+168C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,196 control chromosomes in the GnomAD database, including 4,148 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 0.23 (4148 hom., cov: 33)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5	c.2151+168C>T		intron_variant	Intron 13 of 21	ENST00000617924.6	NP_003238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6	c.2151+168C>T		intron_variant	Intron 13 of 21	1	NM_003247.5	ENSP00000482784.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34238 AN: 152078 Hom.: 4137 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.225 AC: 34300 AN: 152196 Hom.: 4148 Cov.: 33 AF XY: 0.226 AC XY: 16788 AN XY: 74410

African (AFR) AF: 0.303 AC: 12560 AN: 41516

American (AMR) AF: 0.236 AC: 3614 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 570 AN: 3472

East Asian (EAS) AF: 0.222 AC: 1144 AN: 5164

South Asian (SAS) AF: 0.272 AC: 1315 AN: 4834

European-Finnish (FIN) AF: 0.184 AC: 1951 AN: 10604

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.183 AC: 12432 AN: 67996

Other (OTH) AF: 0.222 AC: 469 AN: 2110

Alfa AF: 0.197 Hom.: 11229

Bravo AF: 0.232

Asia WGS AF: 0.287 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.46
PhyloP100		-1.8
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: rs6940420; hg19: chr6-169631907; COSMIC: COSV64681871; COSMIC: COSV64681871;