rs9283850

Positions:

• chr6-169237361-G-A
• chr6-169237361-G-C
• chr6-169237361-G-T

Variant summary

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

The NM_003247.5(THBS2):​c.1301-15C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,611,876 control chromosomes in the GnomAD database, including 234,862 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 0.60 (28058 hom., cov: 35)
  • Exomes 𝑓: 0.53 (206804 hom.)
• Consequence: THBS2 NM_003247.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS2	NM_003247.5	c.1301-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000617924.6
THBS2-AS1	NR_134621.1	n.682-1864G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS2	ENST00000617924.6	c.1301-15C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003247.5	P4
THBS2-AS1	ENST00000660724.1	n.640-1864G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90455 AN: 152070 Hom.: 28017 Cov.: 35

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.611

GnomAD3 exomes AF: 0.572 AC: 142018 AN: 248138 Hom.: 42773 AF XY: 0.558 AC XY: 75182 AN XY: 134624

Gnomad AFR exome AF: 0.732

Gnomad AMR exome AF: 0.695

Gnomad ASJ exome AF: 0.502

Gnomad EAS exome AF: 0.901

Gnomad SAS exome AF: 0.502

Gnomad FIN exome AF: 0.483

Gnomad NFE exome AF: 0.501

Gnomad OTH exome AF: 0.549

GnomAD4 exome AF: 0.526 AC: 767096 AN: 1459688 Hom.: 206804 Cov.: 46 AF XY: 0.523 AC XY: 379971 AN XY: 726120

Gnomad4 AFR exome AF: 0.729

Gnomad4 AMR exome AF: 0.687

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.891

Gnomad4 SAS exome AF: 0.499

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.503

Gnomad4 OTH exome AF: 0.550

GnomAD4 genome AF: 0.595 AC: 90552 AN: 152188 Hom.: 28058 Cov.: 35 AF XY: 0.593 AC XY: 44093 AN XY: 74382

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.612

Alfa AF: 0.529 Hom.: 29745

Bravo AF: 0.617

Asia WGS AF: 0.711 AC: 2471 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	2.1
DANN	Benign	0.57

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: rs9283850; hg19: chr6-169637456; COSMIC: COSV64679995;