VCV002920746.2 - ClinVar

NM_005630.3(SLCO2A1):c.1372G>T (p.Val458Phe)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_005630.3(SLCO2A1):c.1372G>T (p.Val458Phe)

Variation ID: 2920746 Accession: VCV002920746.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3q22.1 3: 133945184 (GRCh38) [ NCBI UCSC ] 3: 133664028 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 20, 2024	Mar 10, 2024	Feb 13, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_005630.3:c.1372G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005621.2:p.Val458Phe	missense
NC_000003.12:g.133945184C>A
NC_000003.11:g.133664028C>A
NG_031964.3:g.112001G>T
NG_077316.1:g.200C>A
LRG_841:g.112001G>T
LRG_841t1:c.1372G>T	LRG_841p1:p.Val458Phe

... more HGVS ... less HGVS

Protein change

Other names

V458F

Canonical SPDI

NC_000003.12:133945183:C:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

OMIM: 601460.0021 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
LOC123038185	-	-	-	GRCh38	-	30
SLCO2A1		-	-	GRCh38 GRCh37	274	310

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Hypertrophic osteoarthropathy, primary, autosomal recessive, 2	Pathogenic (1)	no assertion criteria provided	Feb 13, 2024	RCV003643511.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Feb 13, 2024)	no assertion criteria provided Method: literature only	PHOAR2-ENTEROPATHY SYNDROME Affected status: not provided Allele origin: germline	OMIM Accession: SCV004562038.2 First in ClinVar: Feb 20, 2024 Last updated: Mar 10, 2024	Publications: PubMed (2) PubMed: 26539716‚ 28425581 Comment on evidence: In a 72-year-old Japanese woman (patient 9) who had onset of anemia and hypoproteinemia at age 40 years and was diagnosed with chronic nonspecific multiple … (more) In a 72-year-old Japanese woman (patient 9) who had onset of anemia and hypoproteinemia at age 40 years and was diagnosed with chronic nonspecific multiple ulcers of the ileum at age 66, who also exhibited clubbing of the fingers and periostosis (PHOAR2E; 614441), Umeno et al. (2015) identified homozygosity for a c.1372G-T transversion (c.1372G-T, NM_005630) in exon 10 of the SLCO2A1 gene, resulting in a val458-to-phe (V458F) substitution. Functional analysis in transfected HEK293 cells demonstrated that the V458F mutant was unable take up PGE, indicating loss of function as a PGE transporter. In a 25-year-old Han Chinese man (P26) with pachydermia, digital clubbing, periostosis, and hyperhidrosis, Li et al. (2017) identified homozygosity for the V458F substitution, which occurred at a highly conserved residue and was not found in the ExAC database. The patient was not reported to have had watery diarrhea, gastrointestinal hemorrhage, or anemia; the presence or absence of gastrointestinal ulcers was not sought in this study. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Clinical, Biochemical, and Genetic Features of 41 Han Chinese Families With Primary Hypertrophic Osteoarthropathy, and Their Therapeutic Response to Etoricoxib: Results From a Six-Month Prospective Clinical Intervention.	Li SS	Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research	2017	PMID: 28425581
A Hereditary Enteropathy Caused by Mutations in the SLCO2A1 Gene, Encoding a Prostaglandin Transporter.	Umeno J	PLoS genetics	2015	PMID: 26539716

Text-mined citations for this variant ...

Record last updated Mar 17, 2024

ClinVar Genomic variation as it relates to human health

NM_005630.3(SLCO2A1):c.1372G>T (p.Val458Phe)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...