ClinVar Genomic variation as it relates to human health
NM_001384140.1(PCDH15):c.2138A>G (p.Asn713Ser)
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_001384140.1(PCDH15):c.2138A>G (p.Asn713Ser)
Variation ID: 286893 Accession: VCV000286893.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q21.1 10: 54066839 (GRCh38) [ NCBI UCSC ] 10: 55826599 (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 Dec 6, 2016 Feb 7, 2023 Jan 24, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001384140.1:c.2138A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001371069.1:p.Asn713Ser missense NM_033056.4:c.2138A>G MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_149045.3:p.Asn713Ser missense NM_001142763.2:c.2153A>G NP_001136235.1:p.Asn718Ser missense NM_001142764.2:c.2138A>G NP_001136236.1:p.Asn713Ser missense NM_001142765.2:c.1925A>G NP_001136237.1:p.Asn642Ser missense NM_001142766.2:c.2138A>G NP_001136238.1:p.Asn713Ser missense NM_001142767.2:c.2027A>G NP_001136239.1:p.Asn676Ser missense NM_001142768.2:c.2072A>G NP_001136240.1:p.Asn691Ser missense NM_001142769.3:c.2174A>G NP_001136241.1:p.Asn725Ser missense NM_001142770.3:c.2138A>G NP_001136242.1:p.Asn713Ser missense NM_001142771.2:c.2153A>G NP_001136243.1:p.Asn718Ser missense NM_001142772.2:c.2138A>G NP_001136244.1:p.Asn713Ser missense NM_001142773.2:c.2072A>G NP_001136245.1:p.Asn691Ser missense NM_001354404.2:c.2072A>G NP_001341333.1:p.Asn691Ser missense NM_001354411.2:c.2159A>G NP_001341340.1:p.Asn720Ser missense NM_001354420.2:c.2138A>G NP_001341349.1:p.Asn713Ser missense NM_001354429.2:c.2138A>G NP_001341358.1:p.Asn713Ser missense NM_001354430.2:c.2138A>G NP_001341359.1:p.Asn713Ser missense NC_000010.11:g.54066839T>C NC_000010.10:g.55826599T>C NG_009191.3:g.1567344A>G - Protein change
- N713S, N718S, N725S, N642S, N676S, N691S, N720S
- Other names
- NM_001384140.1(PCDH15):c.2138A>G
- p.Asn713Ser
- Canonical SPDI
- NC_000010.11:54066838:T:C
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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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0.00020 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00003
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
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
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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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PCDH15 | - | - |
GRCh38 GRCh37 |
3379 | 3469 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Jul 11, 2022 | RCV000267122.6 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV000294986.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 24, 2023 | RCV002519268.2 |
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
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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
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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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Uncertain significance
(Mar 16, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000340490.3
First in ClinVar: Dec 06, 2016 Last updated: Apr 03, 2017 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000363197.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Uncertain significance
(Jul 11, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003472901.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 713 of the PCDH15 protein (p.Asn713Ser). … (more)
This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 713 of the PCDH15 protein (p.Asn713Ser). This variant is present in population databases (rs190878515, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of PCDH15-related conditions (PMID: 31054281). This variant is also known as c.2153A>G (p.Asn718Ser). ClinVar contains an entry for this variant (Variation ID: 286893). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Jan 24, 2023)
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criteria provided, single submitter
Method: curation
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Usher syndrome type 1F
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV003761104.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
The p.Asn713Ser variant in PCDH15 has not been previously reported in the literature in individuals with Usher syndrome type 1F but has been identified in … (more)
The p.Asn713Ser variant in PCDH15 has not been previously reported in the literature in individuals with Usher syndrome type 1F but has been identified in 0.005% (1/18380) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs190878515). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 286893) and has been interpreted as a variant of uncertain significance by Eurofins NTD LLC (GA) and Illumina Laboratory Services (Illumina). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Asn713Ser variant is uncertain. ACMG/AMP Criteria applied: PM2_supporting (Richards 2015). (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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Genetic and Clinical Findings in a Large Cohort of Chinese Patients with Suspected Retinitis Pigmentosa. | Gao FJ | Ophthalmology | 2019 | PMID: 31054281 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PCDH15 | - | - | - | - |
Text-mined citations for rs190878515 ...
HelpRecord last updated Jun 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.