6-169222395-G-A

Variant names:

• chr6-169222395-G-A
• rs9505895
• NM_003247.5:c.3075C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_003247.5(THBS2):​c.3075C>T​(p.Ala1025Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,613,452 control chromosomes in the GnomAD database, including 31,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (3550 hom., cov: 33)
  • Exomes 𝑓: 0.19 (28350 hom.)
• Consequence: THBS2 NM_003247.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -5.67
• Publications: 16 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-169222395-G-A is Benign according to our data. Variant chr6-169222395-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059272.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-5.67 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 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.3075C>T	p.Ala1025Ala	synonymous	Exon 19 of 22	NP_003238.2
	THBS2	NM_001381939.1		c.2901C>T	p.Ala967Ala	synonymous	Exon 18 of 21	NP_001368868.1	A0A7I2V585
	THBS2	NM_001381942.1		c.2844C>T	p.Ala948Ala	synonymous	Exon 19 of 22	NP_001368871.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS2	ENST00000617924.6	TSL:1 MANE Select	c.3075C>T	p.Ala1025Ala	synonymous	Exon 19 of 22	ENSP00000482784.1	P35442
	THBS2	ENST00000366787.7	TSL:1	c.3075C>T	p.Ala1025Ala	synonymous	Exon 20 of 23	ENSP00000355751.3	P35442
	THBS2	ENST00000649844.1		c.3090C>T	p.Ala1030Ala	synonymous	Exon 19 of 22	ENSP00000497834.1	A0A3B3ITK0

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32338 AN: 151972 Hom.: 3535 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.203

GnomAD2 exomes AF: 0.204 AC: 51303 AN: 251272 AF XY: 0.202

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.222

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.155

Gnomad FIN exome AF: 0.238

Gnomad NFE exome AF: 0.196

Gnomad OTH exome AF: 0.202

GnomAD4 exome AF: 0.195 AC: 284745 AN: 1461362 Hom.: 28350 Cov.: 36 AF XY: 0.195 AC XY: 141477 AN XY: 726992

African (AFR) AF: 0.254 AC: 8501 AN: 33480

American (AMR) AF: 0.219 AC: 9780 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 5110 AN: 26136

East Asian (EAS) AF: 0.130 AC: 5177 AN: 39698

South Asian (SAS) AF: 0.203 AC: 17509 AN: 86258

European-Finnish (FIN) AF: 0.240 AC: 12714 AN: 52914

Middle Eastern (MID) AF: 0.230 AC: 1328 AN: 5768

European-Non Finnish (NFE) AF: 0.191 AC: 212653 AN: 1112002

Other (OTH) AF: 0.198 AC: 11973 AN: 60390

GnomAD4 genome AF: 0.213 AC: 32386 AN: 152090 Hom.: 3550 Cov.: 33 AF XY: 0.214 AC XY: 15907 AN XY: 74360

African (AFR) AF: 0.248 AC: 10307 AN: 41494

American (AMR) AF: 0.203 AC: 3109 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3472

East Asian (EAS) AF: 0.151 AC: 780 AN: 5178

South Asian (SAS) AF: 0.204 AC: 981 AN: 4814

European-Finnish (FIN) AF: 0.224 AC: 2370 AN: 10578

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.197 AC: 13385 AN: 67966

Other (OTH) AF: 0.204 AC: 430 AN: 2106

Alfa AF: 0.203 Hom.: 1674

Bravo AF: 0.214

Asia WGS AF: 0.222 AC: 769 AN: 3478

EpiCase AF: 0.192

EpiControl AF: 0.189

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	THBS2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.091
DANN	Benign	0.83
PhyloP100		-5.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9505895; hg19: chr6-169622490; COSMIC: COSV64677715;