rs6422747
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_003247.5(THBS2):c.2152-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,606,948 control chromosomes in the GnomAD database, including 286,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.67 ( 36273 hom., cov: 33)
Exomes 𝑓: 0.58 ( 250050 hom. )
Consequence
THBS2
NM_003247.5 splice_polypyrimidine_tract, intron
NM_003247.5 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00002677
2
Clinical Significance
Conservation
PhyloP100: -0.431
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 6-169229688-G-A is Benign according to our data. Variant chr6-169229688-G-A is described in ClinVar as [Benign]. Clinvar id is 3059455.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THBS2 | NM_003247.5 | c.2152-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000617924.6 | |||
THBS2-AS1 | NR_134621.1 | n.682-9537G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THBS2 | ENST00000617924.6 | c.2152-9C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_003247.5 | P4 | |||
THBS2-AS1 | ENST00000660724.1 | n.640-9537G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.673 AC: 102348AN: 151970Hom.: 36203 Cov.: 33
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GnomAD3 exomes AF: 0.612 AC: 153483AN: 250848Hom.: 47997 AF XY: 0.604 AC XY: 81915AN XY: 135552
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GnomAD4 exome AF: 0.583 AC: 847636AN: 1454860Hom.: 250050 Cov.: 28 AF XY: 0.582 AC XY: 421732AN XY: 724158
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GnomAD4 genome ? AF: 0.674 AC: 102481AN: 152088Hom.: 36273 Cov.: 33 AF XY: 0.670 AC XY: 49827AN XY: 74334
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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 submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 17, 2019 | This 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
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at