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6-169221441-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003247.5(THBS2):c.3360T>C(p.Thr1120=) 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 (★).

Frequency

Genomes: 𝑓 0.24 ( 4775 hom., cov: 33)
Exomes 𝑓: 0.20 ( 30590 hom. )

Consequence

THBS2
NM_003247.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.55
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 -15 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=-0.91).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-169221441-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 criteria_provided_single_submitter, 1 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=-5.55 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 = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
THBS2NM_003247.5 linkuse as main transcriptc.3360T>C p.Thr1120= synonymous_variant 20/22 ENST00000617924.6
THBS2-AS1NR_134621.1 linkuse as main transcriptn.681+6954A>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
THBS2ENST00000617924.6 linkuse as main transcriptc.3360T>C p.Thr1120= synonymous_variant 20/221 NM_003247.5 P4
THBS2-AS1ENST00000660724.1 linkuse as main transcriptn.639+6954A>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.243
AC:
36849
AN:
151942
Hom.:
4756
Cov.:
33
show subpopulations
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
show subpopulations
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
show subpopulations
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.243
AC:
36914
AN:
152060
Hom.:
4775
Cov.:
33
AF XY:
0.244
AC XY:
18164
AN XY:
74354
show subpopulations
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

THBS2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 22, 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
-0.91
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

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

Other links and lift over

dbSNP: rs1132742; hg19: chr6-169621536; COSMIC: COSV64677064; API