6-169225695-G-A

Variant names:

• chr6-169225695-G-A
• rs12665573
• NM_003247.5:c.2539-316C>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.2539-316C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,150 control chromosomes in the GnomAD database, including 2,203 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 0.14 (2203 hom., cov: 33)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003247.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS2	NM_003247.5	MANE Select	c.2539-316C>T		intron	N/A	NP_003238.2
	THBS2	NM_001381939.1		c.2365-316C>T		intron	N/A	NP_001368868.1
	THBS2	NM_001381942.1		c.2308-316C>T		intron	N/A	NP_001368871.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS2	ENST00000617924.6	TSL:1 MANE Select	c.2539-316C>T		intron	N/A	ENSP00000482784.1
	THBS2	ENST00000366787.7	TSL:1	c.2539-316C>T		intron	N/A	ENSP00000355751.3
	THBS2	ENST00000649844.1		c.2554-316C>T		intron	N/A	ENSP00000497834.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20810 AN: 152032 Hom.: 2202 Cov.: 33

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0768

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.137 AC: 20836 AN: 152150 Hom.: 2203 Cov.: 33 AF XY: 0.133 AC XY: 9881 AN XY: 74388

African (AFR) AF: 0.294 AC: 12205 AN: 41468

American (AMR) AF: 0.0891 AC: 1362 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3470

East Asian (EAS) AF: 0.131 AC: 675 AN: 5172

South Asian (SAS) AF: 0.0570 AC: 275 AN: 4828

European-Finnish (FIN) AF: 0.0644 AC: 682 AN: 10596

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0768 AC: 5226 AN: 68008

Other (OTH) AF: 0.113 AC: 238 AN: 2110

Alfa AF: 0.0870 Hom.: 419

Bravo AF: 0.146

Asia WGS AF: 0.0970 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.94
PhyloP100		-1.4
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: rs12665573; hg19: chr6-169625790;