rs78602344

chr6-169226486-T-C

Variant summary

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

The NM_003247.5(THBS2):c.2420-188A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 152,282 control chromosomes in the GnomAD database, including 407 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 0.065 (407 hom., cov: 33)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS2	NM_003247.5	c.2420-188A>G		intron_variant		ENST00000617924.6
THBS2-AS1	NR_134621.1	n.681+11999T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS2	ENST00000617924.6	c.2420-188A>G		intron_variant		1	NM_003247.5	P4
THBS2-AS1	ENST00000660724.1	n.639+11999T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0652 AC: 9914 AN: 152164 Hom.: 403 Cov.: 33

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.0830

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.0731

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

GnomAD4 genome AF: 0.0653 AC: 9937 AN: 152282 Hom.: 407 Cov.: 33 AF XY: 0.0682 AC XY: 5081 AN XY: 74470

Gnomad4 AFR AF: 0.0512

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0426

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.0837

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.0757

Alfa AF: 0.0525 Hom.: 59

Bravo AF: 0.0676

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.18
Dann	Benign	0.33

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: rs78602344; hg19: chr6-169626581;