6-169237361-G-A

Variant names:

• chr6-169237361-G-A
• rs9283850
• NM_003247.5:c.1301-15C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003247.5(THBS2):​c.1301-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,611,876 control chromosomes in the GnomAD database, including 234,862 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 0.60 (28058 hom., cov: 35)
  • Exomes 𝑓: 0.53 (206804 hom.)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 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.1301-15C>T		intron	N/A	NP_003238.2
	THBS2	NM_001381939.1		c.1301-15C>T		intron	N/A	NP_001368868.1
	THBS2	NM_001381942.1		c.1070-15C>T		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.1301-15C>T		intron	N/A	ENSP00000482784.1
	THBS2	ENST00000366787.7	TSL:1	c.1301-15C>T		intron	N/A	ENSP00000355751.3
	THBS2	ENST00000461848.1	TSL:2	n.52C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90455 AN: 152070 Hom.: 28017 Cov.: 35

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.611

GnomAD2 exomes AF: 0.572 AC: 142018 AN: 248138 AF XY: 0.558

Gnomad AFR exome AF: 0.732

Gnomad AMR exome AF: 0.695

Gnomad ASJ exome AF: 0.502

Gnomad EAS exome AF: 0.901

Gnomad FIN exome AF: 0.483

Gnomad NFE exome AF: 0.501

Gnomad OTH exome AF: 0.549

GnomAD4 exome AF: 0.526 AC: 767096 AN: 1459688 Hom.: 206804 Cov.: 46 AF XY: 0.523 AC XY: 379971 AN XY: 726120

African (AFR) AF: 0.729 AC: 24416 AN: 33472

American (AMR) AF: 0.687 AC: 30710 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 12968 AN: 26124

East Asian (EAS) AF: 0.891 AC: 35349 AN: 39692

South Asian (SAS) AF: 0.499 AC: 42995 AN: 86228

European-Finnish (FIN) AF: 0.481 AC: 25023 AN: 52002

Middle Eastern (MID) AF: 0.505 AC: 2911 AN: 5768

European-Non Finnish (NFE) AF: 0.503 AC: 559551 AN: 1111356

Other (OTH) AF: 0.550 AC: 33173 AN: 60354

GnomAD4 genome AF: 0.595 AC: 90552 AN: 152188 Hom.: 28058 Cov.: 35 AF XY: 0.593 AC XY: 44093 AN XY: 74382

African (AFR) AF: 0.726 AC: 30178 AN: 41550

American (AMR) AF: 0.633 AC: 9672 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1803 AN: 3470

East Asian (EAS) AF: 0.898 AC: 4639 AN: 5166

South Asian (SAS) AF: 0.516 AC: 2489 AN: 4828

European-Finnish (FIN) AF: 0.479 AC: 5072 AN: 10592

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.510 AC: 34682 AN: 67978

Other (OTH) AF: 0.612 AC: 1294 AN: 2114

Alfa AF: 0.543 Hom.: 69994

Bravo AF: 0.617

Asia WGS AF: 0.711 AC: 2471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.57
PhyloP100		1.2
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: rs9283850; hg19: chr6-169637456; COSMIC: COSV64679995;