6-169221041-T-C

Variant names:

• chr6-169221041-T-C
• rs10945405
• NM_003247.5:c.3371+389A>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.3371+389A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,180 control chromosomes in the GnomAD database, including 30,157 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 0.62 (30157 hom., cov: 34)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58
• Publications: 11 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 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.3371+389A>G		intron	N/A	NP_003238.2
	THBS2	NM_001381939.1		c.3197+389A>G		intron	N/A	NP_001368868.1
	THBS2	NM_001381942.1		c.3140+389A>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.3371+389A>G		intron	N/A	ENSP00000482784.1
	THBS2	ENST00000366787.7	TSL:1	c.3371+389A>G		intron	N/A	ENSP00000355751.3
	THBS2	ENST00000649844.1		c.3386+389A>G		intron	N/A	ENSP00000497834.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94373 AN: 152064 Hom.: 30101 Cov.: 34

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.621 AC: 94487 AN: 152180 Hom.: 30157 Cov.: 34 AF XY: 0.618 AC XY: 45961 AN XY: 74396

African (AFR) AF: 0.752 AC: 31245 AN: 41538

American (AMR) AF: 0.675 AC: 10311 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2098 AN: 3472

East Asian (EAS) AF: 0.472 AC: 2433 AN: 5156

South Asian (SAS) AF: 0.532 AC: 2562 AN: 4820

European-Finnish (FIN) AF: 0.473 AC: 5007 AN: 10590

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38775 AN: 68000

Other (OTH) AF: 0.620 AC: 1310 AN: 2112

Alfa AF: 0.592 Hom.: 68893

Bravo AF: 0.641

Asia WGS AF: 0.538 AC: 1870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.040
DANN	Benign	0.34
PhyloP100		-2.6
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: rs10945405; hg19: chr6-169621136;