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GeneBe

6-169223255-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003247.5(THBS2):c.2994C>T(p.Ile998=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,613,334 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 22 hom., cov: 33)
Exomes 𝑓: 0.00085 ( 11 hom. )

Consequence

THBS2
NM_003247.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.534
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=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-169223255-G-A is Benign according to our data. Variant chr6-169223255-G-A is described in ClinVar as [Benign]. Clinvar id is 787309.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=-0.534 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00822 (1251/152266) while in subpopulation AFR AF= 0.0289 (1202/41536). AF 95% confidence interval is 0.0276. There are 22 homozygotes in gnomad4. There are 551 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1245 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
THBS2NM_003247.5 linkuse as main transcriptc.2994C>T p.Ile998= synonymous_variant 18/22 ENST00000617924.6
THBS2-AS1NR_134621.1 linkuse as main transcriptn.681+8768G>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.2994C>T p.Ile998= synonymous_variant 18/221 NM_003247.5 P4
THBS2-AS1ENST00000660724.1 linkuse as main transcriptn.639+8768G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00818
AC:
1245
AN:
152148
Hom.:
22
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0289
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00203
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00574
GnomAD3 exomes
AF:
0.00221
AC:
555
AN:
250982
Hom.:
5
AF XY:
0.00154
AC XY:
209
AN XY:
135758
show subpopulations
Gnomad AFR exome
AF:
0.0299
Gnomad AMR exome
AF:
0.00124
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000761
Gnomad SAS exome
AF:
0.0000981
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.000847
AC:
1238
AN:
1461068
Hom.:
11
Cov.:
32
AF XY:
0.000731
AC XY:
531
AN XY:
726672
show subpopulations
Gnomad4 AFR exome
AF:
0.0295
Gnomad4 AMR exome
AF:
0.00141
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000328
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000306
Gnomad4 OTH exome
AF:
0.00205
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00822
AC:
1251
AN:
152266
Hom.:
22
Cov.:
33
AF XY:
0.00740
AC XY:
551
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0289
Gnomad4 AMR
AF:
0.00203
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00568
Alfa
AF:
0.00521
Hom.:
5
Bravo
AF:
0.00906
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
0.60
Dann
Benign
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs35671519; hg19: chr6-169623350; API