ClinVar Genomic variation as it relates to human health
NM_001162498.3(LPAR6):c.565G>A (p.Glu189Lys)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001162498.3(LPAR6):c.565G>A (p.Glu189Lys)
Variation ID: 1829 Accession: VCV000001829.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q14.2 13: 48411859 (GRCh38) [ NCBI UCSC ] 13: 48985995 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Jun 12, 2018 Sep 16, 2024 Jun 11, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000321.3:c.1695+30416C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001162498.3:c.565G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001155970.1:p.Glu189Lys missense NM_001162497.3:c.565G>A NP_001155969.1:p.Glu189Lys missense NM_001377316.2:c.565G>A NP_001364245.1:p.Glu189Lys missense NM_001377317.2:c.565G>A NP_001364246.1:p.Glu189Lys missense NM_001407165.1:c.1695+30416C>T intron variant NM_005767.7:c.565G>A NP_005758.2:p.Glu189Lys missense NC_000013.11:g.48411859C>T NC_000013.10:g.48985995C>T NG_009009.1:g.113113C>T NG_012874.1:g.37846G>A NG_012874.2:g.37810G>A NG_127784.1:g.363C>T LRG_517:g.113113C>T P43657:p.Glu189Lys - Protein change
- E189K
- Other names
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- Canonical SPDI
- NC_000013.11:48411858:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
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 | ||
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HI score
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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. |
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RB1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3624 | 3783 | |
LPAR6 | - | - |
GRCh38 GRCh37 |
- | 143 |
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
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jun 11, 2024 | RCV000001903.6 |
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
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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. |
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Pathogenic
(Jun 11, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hypotrichosis 8
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV005204440.1
First in ClinVar: Sep 16, 2024 Last updated: Sep 16, 2024 |
Comment:
Variant summary: LPAR6 c.565G>A (p.Glu189Lys) results in a conservative amino acid change located in the GPCR, rhodopsin-like, 7TM domain (IPR017452) of the encoded protein sequence. … (more)
Variant summary: LPAR6 c.565G>A (p.Glu189Lys) results in a conservative amino acid change located in the GPCR, rhodopsin-like, 7TM domain (IPR017452) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 249012 control chromosomes (gnomAD). c.565G>A has been reported in the literature in several homozygous individuals affected with Woolly hair, autosomal recessive, with or without hypotrichosis (examples: Saleh_2021, Shimomura_2008). These data indicate that the variant is very likely to be associated with disease. In vitro functional studies, suggest that the variant may be defective in ligand binding and/or signaling (Yanagida_2023). The following publications have been ascertained in the context of this evaluation (PMID: 36173926, 18461368, 34374989, 18297072). ClinVar contains an entry for this variant (Variation ID: 1829). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Likely pathogenic
(-)
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criteria provided, single submitter
Method: curation
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Hypotrichosis 8
Affected status: unknown
Allele origin:
unknown
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SIB Swiss Institute of Bioinformatics
Accession: SCV003932426.1
First in ClinVar: Jun 17, 2023 Last updated: Jun 17, 2023 |
Comment:
This variant is interpreted as likely pathogenic for Woolly hair autosomal recessive 1 with or without hypotrichosis. The following ACMG Tag(s) were applied: Absent from … (more)
This variant is interpreted as likely pathogenic for Woolly hair autosomal recessive 1 with or without hypotrichosis. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1); For recessive disorders, detected in trans with a pathogenic variant (PM3); Well-established functional studies show a deleterious effect (PS3 downgraded to supporting); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3). (less)
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Pathogenic
(Jun 01, 2008)
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no assertion criteria provided
Method: literature only
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WOOLLY HAIR, AUTOSOMAL RECESSIVE 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000022060.2
First in ClinVar: Apr 04, 2013 Last updated: Jun 12, 2018 |
Comment on evidence:
In affected members of a Pakistani family with autosomal recessive woolly hair (see 278150), Shimomura et al. (2008) identified a homozygous 565G-A transition in the … (more)
In affected members of a Pakistani family with autosomal recessive woolly hair (see 278150), Shimomura et al. (2008) identified a homozygous 565G-A transition in the P2RY5 gene, resulting in a glu189-to-lys (E189K) substitution in the fifth transmembrane domain. Azeem et al. (2008) identified a homozygous E189K substitution in 3 Pakistani families with autosomal recessive hypotrichosis (278150). The authors noted that none of their patients had woolly hair. (less)
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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
HelpTitle | Author | Journal | Year | Link |
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Cell-trafficking impairment in disease-associated LPA6 missense mutants and a potential pharmacoperone therapy for autosomal recessive woolly hair/hypotrichosis. | Yanagida K | Human molecular genetics | 2023 | PMID: 36173926 |
Spectrum of neuro-genetic disorders in the United Arab Emirates national population. | Saleh S | Clinical genetics | 2021 | PMID: 34374989 |
Novel mutations in G protein-coupled receptor gene (P2RY5) in families with autosomal recessive hypotrichosis (LAH3). | Azeem Z | Human genetics | 2008 | PMID: 18461368 |
Disruption of P2RY5, an orphan G protein-coupled receptor, underlies autosomal recessive woolly hair. | Shimomura Y | Nature genetics | 2008 | PMID: 18297072 |
Text-mined citations for rs121434309 ...
HelpRecord last updated Sep 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.