rs7382358

Variant names:

• chr6-169246927-T-C
• rs7382358
• NM_003247.5:c.610-646A>G

Variant summary

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

The NM_003247.5(THBS2):​c.610-646A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,168 control chromosomes in the GnomAD database, including 4,986 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 0.25 (4986 hom., cov: 33)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396
• 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 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, classic-like, 3

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS2	NM_003247.5	MANE Select	c.610-646A>G		intron	N/A	NP_003238.2
	THBS2	NM_001381939.1		c.610-646A>G		intron	N/A	NP_001368868.1	A0A7I2V585
	THBS2	NM_001381942.1		c.379-646A>G		intron	N/A	NP_001368871.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS2	ENST00000617924.6	TSL:1 MANE Select	c.610-646A>G		intron	N/A	ENSP00000482784.1	P35442
	THBS2	ENST00000366787.7	TSL:1	c.610-646A>G		intron	N/A	ENSP00000355751.3	P35442
	THBS2	ENST00000649844.1		c.610-646A>G		intron	N/A	ENSP00000497834.1	A0A3B3ITK0

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38129 AN: 152052 Hom.: 4979 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.251 AC: 38157 AN: 152168 Hom.: 4986 Cov.: 33 AF XY: 0.254 AC XY: 18933 AN XY: 74398

African (AFR) AF: 0.169 AC: 7026 AN: 41538

American (AMR) AF: 0.259 AC: 3957 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 907 AN: 3466

East Asian (EAS) AF: 0.240 AC: 1242 AN: 5182

South Asian (SAS) AF: 0.345 AC: 1665 AN: 4824

European-Finnish (FIN) AF: 0.318 AC: 3361 AN: 10572

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19010 AN: 67982

Other (OTH) AF: 0.273 AC: 577 AN: 2110

Alfa AF: 0.270 Hom.: 17306

Bravo AF: 0.241

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.33
PhyloP100		-0.40
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: rs7382358; hg19: chr6-169647022;