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GeneBe

6-169220268-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003247.5(THBS2):c.3441C>T(p.Gly1147=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00437 in 1,613,866 control chromosomes in the GnomAD database, including 281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 151 hom., cov: 33)
Exomes 𝑓: 0.0023 ( 130 hom. )

Consequence

THBS2
NM_003247.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0570
Variant links:
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)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-169220268-G-A is Benign according to our data. Variant chr6-169220268-G-A is described in ClinVar as [Benign]. Clinvar id is 787843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.057 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
THBS2NM_003247.5 linkuse as main transcriptc.3441C>T p.Gly1147= synonymous_variant 21/22 ENST00000617924.6
THBS2-AS1NR_134621.1 linkuse as main transcriptn.681+5781G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
THBS2ENST00000617924.6 linkuse as main transcriptc.3441C>T p.Gly1147= synonymous_variant 21/221 NM_003247.5 P4
THBS2-AS1ENST00000660724.1 linkuse as main transcriptn.639+5781G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0238
AC:
3624
AN:
152130
Hom.:
151
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0827
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00922
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:
0.000279
Gnomad OTH
AF:
0.0172
GnomAD3 exomes
AF:
0.00612
AC:
1539
AN:
251416
Hom.:
63
AF XY:
0.00442
AC XY:
601
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.0853
Gnomad AMR exome
AF:
0.00295
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000255
Gnomad OTH exome
AF:
0.00293
GnomAD4 exome
AF:
0.00234
AC:
3425
AN:
1461618
Hom.:
130
Cov.:
33
AF XY:
0.00205
AC XY:
1493
AN XY:
727100
show subpopulations
Gnomad4 AFR exome
AF:
0.0826
Gnomad4 AMR exome
AF:
0.00344
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000186
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000120
Gnomad4 OTH exome
AF:
0.00561
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0239
AC:
3633
AN:
152248
Hom.:
151
Cov.:
33
AF XY:
0.0225
AC XY:
1679
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.0827
Gnomad4 AMR
AF:
0.00921
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.0171
Alfa
AF:
0.00803
Hom.:
26
Bravo
AF:
0.0266
Asia WGS
AF:
0.00520
AC:
18
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000415

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -
THBS2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesApr 11, 2019This 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
-0.59
Cadd
Benign
2.5
Dann
Benign
0.84

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs59953407; hg19: chr6-169620363; COSMIC: COSV64677242; API