rs9505888

Variant names:

• chr6-169225779-A-G
• rs9505888
• NM_003247.5:c.2539-400T>C

Variant summary

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

The NM_003247.5(THBS2):​c.2539-400T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,068 control chromosomes in the GnomAD database, including 24,605 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 0.56 (24605 hom., cov: 33)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973
• 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-AS1 (HGNC:56059): (THBS2 antisense RNA 1)

LOC124901470 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5	c.2539-400T>C		intron_variant	Intron 16 of 21	ENST00000617924.6	NP_003238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6	c.2539-400T>C		intron_variant	Intron 16 of 21	1	NM_003247.5	ENSP00000482784.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85754 AN: 151950 Hom.: 24583 Cov.: 33

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.564 AC: 85817 AN: 152068 Hom.: 24605 Cov.: 33 AF XY: 0.559 AC XY: 41527 AN XY: 74334

African (AFR) AF: 0.537 AC: 22242 AN: 41456

American (AMR) AF: 0.578 AC: 8849 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2075 AN: 3468

East Asian (EAS) AF: 0.311 AC: 1605 AN: 5162

South Asian (SAS) AF: 0.513 AC: 2478 AN: 4826

European-Finnish (FIN) AF: 0.508 AC: 5362 AN: 10562

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41211 AN: 67978

Other (OTH) AF: 0.587 AC: 1239 AN: 2112

Alfa AF: 0.595 Hom.: 37739

Bravo AF: 0.569

Asia WGS AF: 0.464 AC: 1612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.53
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9505888; hg19: chr6-169625874;