rs776813259
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1_ModeratePP5_Very_Strong
The NM_005630.3(SLCO2A1):c.1807C>T(p.Arg603Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000131 in 1,603,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
SLCO2A1
NM_005630.3 stop_gained
NM_005630.3 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 3.62
Genes affected
SLCO2A1 (HGNC:10955): (solute carrier organic anion transporter family member 2A1) This gene encodes a prostaglandin transporter that is a member of the 12-membrane-spanning superfamily of transporters. The encoded protein may be involved in mediating the uptake and clearance of prostaglandins in numerous tissues. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0647 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PP5
?
Variant 3-133935781-G-A is Pathogenic according to our data. Variant chr3-133935781-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 225477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLCO2A1 | NM_005630.3 | c.1807C>T | p.Arg603Ter | stop_gained | 13/14 | ENST00000310926.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLCO2A1 | ENST00000310926.11 | c.1807C>T | p.Arg603Ter | stop_gained | 13/14 | 1 | NM_005630.3 | P1 | |
SLCO2A1 | ENST00000493729.5 | c.1579C>T | p.Arg527Ter | stop_gained | 12/13 | 5 | |||
SLCO2A1 | ENST00000481359.3 | c.*369C>T | 3_prime_UTR_variant, NMD_transcript_variant | 12/13 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000364 AC: 9AN: 247052Hom.: 0 AF XY: 0.0000300 AC XY: 4AN XY: 133428
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GnomAD4 exome AF: 0.0000138 AC: 20AN: 1451116Hom.: 0 Cov.: 30 AF XY: 0.0000139 AC XY: 10AN XY: 721762
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hypertrophic osteoarthropathy, primary, autosomal recessive, 2 Pathogenic:3
Likely pathogenic, criteria provided, single submitter | clinical testing | 3billion | Mar 22, 2022 | Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by less than 10% . The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000225477, PMID:24153155). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency:0.0000364). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. - |
Pathogenic, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 13, 2024 | - - |
Hypertrophic osteoarthropathy, primary, autosomal dominant Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 13, 2024 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 03, 2022 | ClinVar contains an entry for this variant (Variation ID: 225477). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with hypertrophic osteoarthropathy (PMID: 24153155, 24929850). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs776813259, gnomAD 0.03%). This sequence change creates a premature translational stop signal (p.Arg603*) in the SLCO2A1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 41 amino acid(s) of the SLCO2A1 protein. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;D
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at