rs387907297
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_005630.3(SLCO2A1):c.310G>T(p.Gly104*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,748 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
SLCO2A1
NM_005630.3 stop_gained
NM_005630.3 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 7.39
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 undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
Variant 3-133973750-C-A is Pathogenic according to our data. Variant chr3-133973750-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 37171.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-133973750-C-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLCO2A1 | NM_005630.3 | c.310G>T | p.Gly104* | stop_gained | 3/14 | ENST00000310926.11 | NP_005621.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLCO2A1 | ENST00000310926.11 | c.310G>T | p.Gly104* | stop_gained | 3/14 | 1 | NM_005630.3 | ENSP00000311291.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251038Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135668
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461748Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3AN XY: 727140
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hypertrophic osteoarthropathy, primary, autosomal dominant Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2012 | - - |
Hypertrophic osteoarthropathy, primary, autosomal recessive, 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2012 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 04, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 37171). This premature translational stop signal has been observed in individuals with clinical features of primary hypertrophic osteoarthropathy (PMID: 22553128, 22906430). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Gly104*) in the SLCO2A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLCO2A1 are known to be pathogenic (PMID: 22553128, 23509104). - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
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