ClinVar Genomic variation as it relates to human health
NM_001162498.3(LPAR6):c.66_69dup (p.Phe24fs)
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.66_69dup (p.Phe24fs)
Variation ID: 1323245 Accession: VCV001323245.8
- Type and length
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Duplication, 4 bp
- Location
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Cytogenetic: 13q14.2 13: 48412354-48412355 (GRCh38) [ NCBI UCSC ] 13: 48986490-48986491 (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 Apr 4, 2013 Dec 17, 2023 Mar 1, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000321.3:c.1695+30914_1695+30917dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001162498.3:c.66_69dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001155970.1:p.Phe24fs frameshift NM_001162497.3:c.66_69dup NP_001155969.1:p.Phe24fs frameshift NM_001377316.2:c.66_69dup NP_001364245.1:p.Phe24fs frameshift NM_001377317.2:c.66_69dup NP_001364246.1:p.Phe24fs frameshift NM_005767.7:c.66_69dup NP_005758.2:p.Phe24fs frameshift NC_000013.11:g.48412357_48412360dup NC_000013.10:g.48986493_48986496dup NG_009009.1:g.113611_113614dup NG_012874.1:g.37347_37350dup LRG_517:g.113611_113614dup - Protein change
- F24fs
- Other names
- p.Phe24HisfsTer29
- Canonical SPDI
- NC_000013.11:48412354:CATGCA:CATGCATGCA
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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.
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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 |
3316 | 3467 | |
LPAR6 | - | - |
GRCh38 GRCh37 |
- | 136 |
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. |
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Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2023 | RCV001783609.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 26, 2022 | RCV001823308.2 | |
Pathogenic (1) |
no assertion criteria provided
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Aug 1, 2011 | RCV002273832.1 |
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. |
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Pathogenic
(Nov 24, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hypotrichosis 8
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV002761192.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
Comment:
A homozygous 4 base pair duplication in exon 1 of the LPAR6 gene that results in a frameshift and premature truncation of the protein 29 … (more)
A homozygous 4 base pair duplication in exon 1 of the LPAR6 gene that results in a frameshift and premature truncation of the protein 29 amino acids downstream to codon 24 was detected.This variant has not been reported in the 1000 genomes and gnomAD databases. The reference region is conserved across species. In summary, the variant meets our criteria to be classified as pathogenic. (less)
Clinical Features:
Absent eyebrow (present)
Age: 50-59 years
Sex: female
Method: DNA was used to perform targeted gene capture using a custom capture kit. Libraries were sequenced to mean >80-100X coverage on the Illumina sequencing platform. Sequence obtained were aligned to human references genome using BWA program and analyzed using Picard and GATK-Lite toolkit to identify variants in the targeted genes relevant to clinical indication.
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Pathogenic
(Jan 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV002072798.2
First in ClinVar: Feb 04, 2022 Last updated: Mar 04, 2023 |
Comment:
Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 321 amino acids are lost and replaced with 28 incorrect amino … (more)
Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 321 amino acids are lost and replaced with 28 incorrect amino acids (HGMD); This variant is associated with the following publications: (PMID: 22385360, 18297072, 28425126, 21426374) (less)
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Pathogenic
(Mar 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hypotrichosis 8
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004176596.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
Comment:
The frameshift variant c.66_69dup(p.Phe24HisfsTer29) in LPAR6 gene has been reported previously in homozygous state in multiple individuals with woolly hair and/or hypotrichosis. This variant is … (more)
The frameshift variant c.66_69dup(p.Phe24HisfsTer29) in LPAR6 gene has been reported previously in homozygous state in multiple individuals with woolly hair and/or hypotrichosis. This variant is considered to have a founder effect in Pakistani patients (Kurban M, et al., 2013, Khan S, et al., 2011). The variant has 0.005% allele frequency in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant causes a frameshift starting with codon Phenylalanine 24, changes this amino acid to Histidine residue, and creates a premature Stop codon at position 29 of the new reading frame, denoted p.Phe24HisfsTer29. This variant has been reported to the ClinVar database as Pathogenic. This frameshift variant in the C-terminus is predicted to result in protein truncation, as the last 321 amino acids are lost and replaced with 28 incorrect amino acids. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Abnormality of the skin (present)
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Pathogenic
(Aug 01, 2011)
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no assertion criteria provided
Method: literature only
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WOOLLY HAIR, AUTOSOMAL RECESSIVE 1, WITH OR WITHOUT HYPOTRICHOSIS
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000022056.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In 4 affected members of a consanguineous Pakistani family with woolly hair and varying degrees of hypotrichosis or sparse hair (see 278150), Shimomura et al. … (more)
In 4 affected members of a consanguineous Pakistani family with woolly hair and varying degrees of hypotrichosis or sparse hair (see 278150), Shimomura et al. (2008) identified homozygosity for a 4-bp insertion (69insCATG) in the LPAR6 gene that was not found in 2 unaffected family members. In affected members of 3 Pakistani families with autosomal recessive localized hypotrichosis-3 (HYPT8; 278150), Azeem et al. (2008) identified homozygosity for the 69insCATG mutation in the LPAR6 gene, predicted to result in protein termination at residue 52. The authors noted that none of their patients had woolly hair. In affected members of 2 Pakistani families segregating an autosomal recessive hypotrichosis/woolly hair phenotype, Khan et al. (2011) identified homozygosity for a 4-bp insertion in the LPAR6 gene that they designated 66_69insCATG. Affected individuals from 1 of the families had features of hypotrichosis, whereas those from the other family exhibited features of woolly hair, with sparse to absent eyebrows, eyelashes, and body hair. Haplotype analysis in the 2 families, which belonged to different ethnic groups from various regions of Pakistan, suggested that the 4-bp insertion was a founder mutation. (less)
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Pathogenic
(Aug 01, 2011)
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no assertion criteria provided
Method: literature only
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HYPOTRICHOSIS 8
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000045050.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In 4 affected members of a consanguineous Pakistani family with woolly hair and varying degrees of hypotrichosis or sparse hair (see 278150), Shimomura et al. … (more)
In 4 affected members of a consanguineous Pakistani family with woolly hair and varying degrees of hypotrichosis or sparse hair (see 278150), Shimomura et al. (2008) identified homozygosity for a 4-bp insertion (69insCATG) in the LPAR6 gene that was not found in 2 unaffected family members. In affected members of 3 Pakistani families with autosomal recessive localized hypotrichosis-3 (HYPT8; 278150), Azeem et al. (2008) identified homozygosity for the 69insCATG mutation in the LPAR6 gene, predicted to result in protein termination at residue 52. The authors noted that none of their patients had woolly hair. In affected members of 2 Pakistani families segregating an autosomal recessive hypotrichosis/woolly hair phenotype, Khan et al. (2011) identified homozygosity for a 4-bp insertion in the LPAR6 gene that they designated 66_69insCATG. Affected individuals from 1 of the families had features of hypotrichosis, whereas those from the other family exhibited features of woolly hair, with sparse to absent eyebrows, eyelashes, and body hair. Haplotype analysis in the 2 families, which belonged to different ethnic groups from various regions of Pakistan, suggested that the 4-bp insertion was a founder mutation. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Hypotrichosis 8
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
biparental
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Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
Accession: SCV002319211.1
First in ClinVar: Apr 02, 2022 Last updated: Apr 02, 2022 |
Age: 10-19 years
Sex: male
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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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Mutations in the LPAR6 and LIPH genes underlie autosomal recessive hypotrichosis/woolly hair in 17 consanguineous families from Pakistan. | Khan S | Clinical and experimental dermatology | 2011 | PMID: 21426374 |
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 rs558917628 ...
HelpRecord last updated Apr 15, 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.