chr3-133935781-G-A

Position:

chr3-133935781-G-A

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

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:5

Conservation

PhyloP100: 3.62

Variant links:

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]

SLCO2A1 links:

Genome browser will be placed here

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 linkuse as main transcript	c.1807C>T	p.Arg603Ter	stop_gained	13/14	ENST00000310926.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLCO2A1	ENST00000310926.11 linkuse as main transcript	c.1807C>T	p.Arg603Ter	stop_gained	13/14	1	NM_005630.3	P1
SLCO2A1	ENST00000493729.5 linkuse as main transcript	c.1579C>T	p.Arg527Ter	stop_gained	12/13	5
SLCO2A1	ENST00000481359.3 linkuse as main transcript	c.*369C>T		3_prime_UTR_variant, NMD_transcript_variant	12/13	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000364

AC:

AN:

247052

Hom.:

AF XY:

0.0000300

AC XY:

AN XY:

133428

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.000276

Gnomad SAS exome

AF:

0.0000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1451116

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

721762

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000278

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000362

Gnomad4 OTH exome

AF:

0.0000669

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000544

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000494

AC:

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

Labcorp Genetics (formerly Invitae), Labcorp

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.42

BayesDel_noAF

Pathogenic

0.59

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.88

MutationTaster

Benign

1.0

D;D

Vest4

0.93

GERP RS

3.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over