6-169222230-G-A

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.3240C>T(p.Asn1080=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0047 in 1,612,422 control chromosomes in the GnomAD database, including 277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (145 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (132 hom.)
• Consequence: THBS2 NM_003247.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.532

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=-0.58).
• BP6: Variant 6-169222230-G-A is Benign according to our data. Variant chr6-169222230-G-A is described in ClinVar as [Benign]. Clinvar id is 711868.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.532 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.3240C>T	p.Asn1080=	synonymous_variant	19/22	ENST00000617924.6
THBS2-AS1	NR_134621.1	n.681+7743G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS2	ENST00000617924.6	c.3240C>T	p.Asn1080=	synonymous_variant	19/22	1	NM_003247.5	P4
THBS2-AS1	ENST00000660724.1	n.639+7743G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3620 AN: 152140 Hom.: 145 Cov.: 33

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00909

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.00645 AC: 1602 AN: 248292 Hom.: 62 AF XY: 0.00478 AC XY: 643 AN XY: 134540

Gnomad AFR exome AF: 0.0836

Gnomad AMR exome AF: 0.00341

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.000187

Gnomad NFE exome AF: 0.000801

Gnomad OTH exome AF: 0.00378

GnomAD4 exome AF: 0.00270 AC: 3945 AN: 1460164 Hom.: 132 Cov.: 32 AF XY: 0.00242 AC XY: 1755 AN XY: 726314

Gnomad4 AFR exome AF: 0.0817

Gnomad4 AMR exome AF: 0.00385

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000406

Gnomad4 FIN exome AF: 0.000230

Gnomad4 NFE exome AF: 0.000528

Gnomad4 OTH exome AF: 0.00613

GnomAD4 genome AF: 0.0238 AC: 3629 AN: 152258 Hom.: 145 Cov.: 33 AF XY: 0.0226 AC XY: 1684 AN XY: 74454

Gnomad4 AFR AF: 0.0819

Gnomad4 AMR AF: 0.00908

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0109 Hom.: 30

Bravo AF: 0.0265

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.00124

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	5.8
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs33925221; hg19: chr6-169622325;