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6-169222395-G-A

Variant summary

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

The NM_003247.5(THBS2):c.3075C>T(p.Ala1025=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,613,452 control chromosomes in the GnomAD database, including 31,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.21 ( 3550 hom., cov: 33)
Exomes 𝑓: 0.19 ( 28350 hom. )

Consequence

THBS2
NM_003247.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.67
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=-0.88).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-169222395-G-A is Benign according to our data. Variant chr6-169222395-G-A is described in ClinVar as [Benign]. Clinvar id is 3059272.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=-5.67 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 = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
THBS2NM_003247.5 linkuse as main transcriptc.3075C>T p.Ala1025= synonymous_variant 19/22 ENST00000617924.6
THBS2-AS1NR_134621.1 linkuse as main transcriptn.681+7908G>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.3075C>T p.Ala1025= synonymous_variant 19/221 NM_003247.5 P4
THBS2-AS1ENST00000660724.1 linkuse as main transcriptn.639+7908G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.213
AC:
32338
AN:
151972
Hom.:
3535
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.248
Gnomad AMI
AF:
0.328
Gnomad AMR
AF:
0.203
Gnomad ASJ
AF:
0.188
Gnomad EAS
AF:
0.151
Gnomad SAS
AF:
0.204
Gnomad FIN
AF:
0.224
Gnomad MID
AF:
0.255
Gnomad NFE
AF:
0.197
Gnomad OTH
AF:
0.203
GnomAD3 exomes
AF:
0.204
AC:
51303
AN:
251272
Hom.:
5294
AF XY:
0.202
AC XY:
27486
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.247
Gnomad AMR exome
AF:
0.222
Gnomad ASJ exome
AF:
0.194
Gnomad EAS exome
AF:
0.155
Gnomad SAS exome
AF:
0.201
Gnomad FIN exome
AF:
0.238
Gnomad NFE exome
AF:
0.196
Gnomad OTH exome
AF:
0.202
GnomAD4 exome
AF:
0.195
AC:
284745
AN:
1461362
Hom.:
28350
Cov.:
36
AF XY:
0.195
AC XY:
141477
AN XY:
726992
show subpopulations
Gnomad4 AFR exome
AF:
0.254
Gnomad4 AMR exome
AF:
0.219
Gnomad4 ASJ exome
AF:
0.196
Gnomad4 EAS exome
AF:
0.130
Gnomad4 SAS exome
AF:
0.203
Gnomad4 FIN exome
AF:
0.240
Gnomad4 NFE exome
AF:
0.191
Gnomad4 OTH exome
AF:
0.198
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.213
AC:
32386
AN:
152090
Hom.:
3550
Cov.:
33
AF XY:
0.214
AC XY:
15907
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.248
Gnomad4 AMR
AF:
0.203
Gnomad4 ASJ
AF:
0.188
Gnomad4 EAS
AF:
0.151
Gnomad4 SAS
AF:
0.204
Gnomad4 FIN
AF:
0.224
Gnomad4 NFE
AF:
0.197
Gnomad4 OTH
AF:
0.204
Alfa
AF:
0.202
Hom.:
1642
Bravo
AF:
0.214
Asia WGS
AF:
0.222
AC:
769
AN:
3478
EpiCase
AF:
0.192
EpiControl
AF:
0.189

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 23, 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
-0.88
Cadd
Benign
0.091
Dann
Benign
0.83

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

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

Other links and lift over

dbSNP: rs9505895; hg19: chr6-169622490; COSMIC: COSV64677715; API