6-169221447-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_003247.5(THBS2):c.3354C>G(p.Pro1118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00447 in 1,613,940 control chromosomes in the GnomAD database, including 273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (143 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (130 hom.)
• Consequence: THBS2 NM_003247.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-169221447-G-C is Benign according to our data. Variant chr6-169221447-G-C is described in ClinVar as [Benign]. Clinvar id is 711867.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS2	NM_003247.5	c.3354C>G	p.Pro1118=	synonymous_variant	20/22	ENST00000617924.6
THBS2-AS1	NR_134621.1	n.681+6960G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS2	ENST00000617924.6	c.3354C>G	p.Pro1118=	synonymous_variant	20/22	1	NM_003247.5	P4
THBS2-AS1	ENST00000660724.1	n.639+6960G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3598 AN: 152130 Hom.: 143 Cov.: 33

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.00621 AC: 1562 AN: 251424 Hom.: 62 AF XY: 0.00455 AC XY: 618 AN XY: 135910

Gnomad AFR exome AF: 0.0836

Gnomad AMR exome AF: 0.00335

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000501

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00247 AC: 3609 AN: 1461692 Hom.: 130 Cov.: 31 AF XY: 0.00217 AC XY: 1581 AN XY: 727156

Gnomad4 AFR exome AF: 0.0814

Gnomad4 AMR exome AF: 0.00385

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000272

Gnomad4 OTH exome AF: 0.00590

GnomAD4 genome AF: 0.0237 AC: 3607 AN: 152248 Hom.: 143 Cov.: 33 AF XY: 0.0224 AC XY: 1667 AN XY: 74446

Gnomad4 AFR AF: 0.0819

Gnomad4 AMR AF: 0.00889

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.00713 Hom.: 8

Bravo AF: 0.0263

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.2
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61730648; hg19: chr6-169621542;