6-169229766-G-C

Variant names:

• chr6-169229766-G-C
• rs9505891
• NM_003247.5:c.2152-87C>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.2152-87C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,083,938 control chromosomes in the GnomAD database, including 27,060 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 0.26 (5899 hom., cov: 33)
  • Exomes 𝑓: 0.20 (21161 hom.)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 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.2152-87C>G		intron	N/A	NP_003238.2
	THBS2	NM_001381939.1		c.1978-87C>G		intron	N/A	NP_001368868.1
	THBS2	NM_001381942.1		c.1921-87C>G		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.2152-87C>G		intron	N/A	ENSP00000482784.1
	THBS2	ENST00000366787.7	TSL:1	c.2152-87C>G		intron	N/A	ENSP00000355751.3
	THBS2	ENST00000649844.1		c.2167-87C>G		intron	N/A	ENSP00000497834.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39846 AN: 151892 Hom.: 5883 Cov.: 33

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.204 AC: 190355 AN: 931928 Hom.: 21161 AF XY: 0.203 AC XY: 97223 AN XY: 478908

African (AFR) AF: 0.401 AC: 9254 AN: 23060

American (AMR) AF: 0.327 AC: 13094 AN: 40030

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 3455 AN: 20804

East Asian (EAS) AF: 0.338 AC: 12391 AN: 36634

South Asian (SAS) AF: 0.215 AC: 15167 AN: 70390

European-Finnish (FIN) AF: 0.242 AC: 10279 AN: 42464

Middle Eastern (MID) AF: 0.225 AC: 1053 AN: 4690

European-Non Finnish (NFE) AF: 0.179 AC: 116307 AN: 651042

Other (OTH) AF: 0.219 AC: 9355 AN: 42814

GnomAD4 genome AF: 0.263 AC: 39918 AN: 152010 Hom.: 5899 Cov.: 33 AF XY: 0.264 AC XY: 19622 AN XY: 74300

African (AFR) AF: 0.394 AC: 16333 AN: 41424

American (AMR) AF: 0.269 AC: 4108 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 580 AN: 3462

East Asian (EAS) AF: 0.357 AC: 1843 AN: 5158

South Asian (SAS) AF: 0.226 AC: 1089 AN: 4812

European-Finnish (FIN) AF: 0.239 AC: 2529 AN: 10560

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12568 AN: 67988

Other (OTH) AF: 0.259 AC: 547 AN: 2110

Alfa AF: 0.106 Hom.: 153

Bravo AF: 0.274

Asia WGS AF: 0.325 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.90
DANN	Benign	0.46
PhyloP100		-0.74
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: rs9505891; hg19: chr6-169629861; COSMIC: COSV64677754; COSMIC: COSV64677754;