rs6422748

Positions:

• chr6-169229815-G-C

Variant summary

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

The NM_003247.5(THBS2):​c.2152-136C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 641,872 control chromosomes in the GnomAD database, including 118,137 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 0.65 (33210 hom., cov: 32)
  • Exomes 𝑓: 0.58 (84927 hom.)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.19

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS2	NM_003247.5	c.2152-136C>G		intron_variant		ENST00000617924.6
THBS2-AS1	NR_134621.1	n.682-9410G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS2	ENST00000617924.6	c.2152-136C>G		intron_variant		1	NM_003247.5	P4
THBS2-AS1	ENST00000660724.1	n.640-9410G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98795 AN: 151970 Hom.: 33145 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.650

GnomAD4 exome AF: 0.583 AC: 285575 AN: 489784 Hom.: 84927 AF XY: 0.583 AC XY: 149327 AN XY: 256126

Gnomad4 AFR exome AF: 0.838

Gnomad4 AMR exome AF: 0.657

Gnomad4 ASJ exome AF: 0.669

Gnomad4 EAS exome AF: 0.549

Gnomad4 SAS exome AF: 0.600

Gnomad4 FIN exome AF: 0.525

Gnomad4 NFE exome AF: 0.566

Gnomad4 OTH exome AF: 0.616

GnomAD4 genome AF: 0.650 AC: 98922 AN: 152088 Hom.: 33210 Cov.: 32 AF XY: 0.648 AC XY: 48203 AN XY: 74338

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.654

Alfa AF: 0.614 Hom.: 3601

Bravo AF: 0.669

Asia WGS AF: 0.659 AC: 2293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.31

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: rs6422748; hg19: chr6-169629910;