6-169222254-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003247.5(THBS2):c.3216G>A(p.Thr1072=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000547 in 1,613,192 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00071 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00053 (1 hom.)
• Consequence: THBS2 NM_003247.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.61

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 6-169222254-C-T is Benign according to our data. Variant chr6-169222254-C-T is described in ClinVar as [Benign]. Clinvar id is 747332.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.61 with no splicing effect.
• BS2: High AC in GnomAd at 108 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS2	NM_003247.5	c.3216G>A	p.Thr1072=	synonymous_variant	19/22	ENST00000617924.6
THBS2-AS1	NR_134621.1	n.681+7767C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS2	ENST00000617924.6	c.3216G>A	p.Thr1072=	synonymous_variant	19/22	1	NM_003247.5	P4
THBS2-AS1	ENST00000660724.1	n.639+7767C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000710 AC: 108 AN: 152190 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000853

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.000953 AC: 238 AN: 249804 Hom.: 1 AF XY: 0.000923 AC XY: 125 AN XY: 135370

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00518

Gnomad NFE exome AF: 0.000961

Gnomad OTH exome AF: 0.00262

GnomAD4 exome AF: 0.000530 AC: 774 AN: 1460884 Hom.: 1 Cov.: 32 AF XY: 0.000488 AC XY: 355 AN XY: 726752

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00570

Gnomad4 NFE exome AF: 0.000382

Gnomad4 OTH exome AF: 0.000745

GnomAD4 genome AF: 0.000709 AC: 108 AN: 152308 Hom.: 1 Cov.: 33 AF XY: 0.000765 AC XY: 57 AN XY: 74476

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.000853

Gnomad4 OTH AF: 0.000475

Alfa AF: 0.000656 Hom.: 0

Bravo AF: 0.000242

EpiCase AF: 0.000436

EpiControl AF: 0.000474

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	-0.67
Cadd	Benign	1.5
Dann	Benign	0.90

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: rs142051087; hg19: chr6-169622349;