6-169221441-A-G

Variant names:

• chr6-169221441-A-G
• rs1132742
• NM_003247.5:c.3360T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_003247.5(THBS2):​c.3360T>C​(p.Thr1120Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,613,474 control chromosomes in the GnomAD database, including 35,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.24 (4775 hom., cov: 33)
  • Exomes 𝑓: 0.20 (30590 hom.)
• Consequence: THBS2 NM_003247.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -5.55

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-169221441-A-G is Benign according to our data. Variant chr6-169221441-A-G is described in ClinVar as [Benign]. Clinvar id is 3060730.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-5.55 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5	c.3360T>C	p.Thr1120Thr	synonymous_variant	Exon 20 of 22	ENST00000617924.6	NP_003238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6	c.3360T>C	p.Thr1120Thr	synonymous_variant	Exon 20 of 22	1	NM_003247.5	ENSP00000482784.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36849 AN: 151942 Hom.: 4756 Cov.: 33

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.227

GnomAD3 exomes AF: 0.220 AC: 55427 AN: 251372 Hom.: 6297 AF XY: 0.216 AC XY: 29385 AN XY: 135868

Gnomad AFR exome AF: 0.330

Gnomad AMR exome AF: 0.242

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.247

Gnomad SAS exome AF: 0.206

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.197

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.201 AC: 294380 AN: 1461414 Hom.: 30590 Cov.: 32 AF XY: 0.201 AC XY: 146073 AN XY: 727040

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.227

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.243 AC: 36914 AN: 152060 Hom.: 4775 Cov.: 33 AF XY: 0.244 AC XY: 18164 AN XY: 74354

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.228

Alfa AF: 0.214 Hom.: 1969

Bravo AF: 0.248

Asia WGS AF: 0.259 AC: 899 AN: 3478

EpiCase AF: 0.194

EpiControl AF: 0.190

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

THBS2-related disorder Benign:1

Aug 02, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.034
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1132742; hg19: chr6-169621536; COSMIC: COSV64677064;