rs12665573

Positions:

• chr6-169225695-G-A
• chr6-169225695-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000617924.6(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 ENST00000617924.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THBS2	NM_003247.5	c.2539-316C>T		intron_variant		ENST00000617924.6	NP_003238.2
THBS2-AS1	NR_134621.1	n.681+11208G>A		intron_variant, non_coding_transcript_variant
LOC124901470	XR_007059889.1	n.314+31G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6	c.2539-316C>T		intron_variant		1	NM_003247.5	ENSP00000482784	P4
THBS2-AS1	ENST00000660724.1	n.639+11208G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.0891

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.0570

Gnomad4 FIN AF: 0.0644

Gnomad4 NFE AF: 0.0768

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0871 Hom.: 388

Bravo AF: 0.146

Asia WGS AF: 0.0970 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.94

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

Publications

LitVar

Other links and lift over

dbSNP: rs12665573; hg19: chr6-169625790;