ClinVar Genomic variation as it relates to human health
NM_001384140.1(PCDH15):c.1205G>C (p.Gly402Ala)
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.
Uncertain significance(6); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001384140.1(PCDH15):c.1205G>C (p.Gly402Ala)
Variation ID: 281800 Accession: VCV000281800.27
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q21.1 10: 54195783 (GRCh38) [ NCBI UCSC ] 10: 55955543 (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 9, 2018 Feb 14, 2024 Jan 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001384140.1:c.1205G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001371069.1:p.Gly402Ala missense NM_033056.4:c.1205G>C MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_149045.3:p.Gly402Ala missense NM_001142763.2:c.1220G>C NP_001136235.1:p.Gly407Ala missense NM_001142764.2:c.1205G>C NP_001136236.1:p.Gly402Ala missense NM_001142765.2:c.1205G>C NP_001136237.1:p.Gly402Ala missense NM_001142766.2:c.1205G>C NP_001136238.1:p.Gly402Ala missense NM_001142767.2:c.1094G>C NP_001136239.1:p.Gly365Ala missense NM_001142768.2:c.1139G>C NP_001136240.1:p.Gly380Ala missense NM_001142769.3:c.1220G>C NP_001136241.1:p.Gly407Ala missense NM_001142770.3:c.1205G>C NP_001136242.1:p.Gly402Ala missense NM_001142771.2:c.1220G>C NP_001136243.1:p.Gly407Ala missense NM_001142772.2:c.1205G>C NP_001136244.1:p.Gly402Ala missense NM_001142773.2:c.1139G>C NP_001136245.1:p.Gly380Ala missense NM_001354404.2:c.1139G>C NP_001341333.1:p.Gly380Ala missense NM_001354411.2:c.1205G>C NP_001341340.1:p.Gly402Ala missense NM_001354420.2:c.1205G>C NP_001341349.1:p.Gly402Ala missense NM_001354429.2:c.1205G>C NP_001341358.1:p.Gly402Ala missense NM_001354430.2:c.1205G>C NP_001341359.1:p.Gly402Ala missense NC_000010.11:g.54195783C>G NC_000010.10:g.55955543C>G NG_009191.3:g.1438400G>C - Protein change
- G407A, G402A, G380A, G365A
- Other names
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- Canonical SPDI
- NC_000010.11:54195782:C:G
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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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0.00140 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00041
Exome Aggregation Consortium (ExAC) 0.00046
The Genome Aggregation Database (gnomAD) 0.00081
Trans-Omics for Precision Medicine (TOPMed) 0.00091
1000 Genomes Project 0.00140
1000 Genomes Project 30x 0.00141
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00146
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
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. |
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PCDH15 | - | - |
GRCh38 GRCh37 |
3319 | 3406 |
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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Uncertain significance (1) |
criteria provided, single submitter
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Dec 21, 2017 | RCV000323966.7 | |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
|
Jan 29, 2024 | RCV000724967.19 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 31, 2018 | RCV000763658.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV001103157.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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May 18, 2021 | RCV001526428.1 |
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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Uncertain significance
(Jul 10, 2015)
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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: SCV000332789.3
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(Oct 31, 2018)
|
criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 1D
Usher syndrome type 1F Autosomal recessive nonsyndromic hearing loss 23
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000894538.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Uncertain significance
(Dec 21, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000711190.2
First in ClinVar: Apr 09, 2018 Last updated: Dec 15, 2018 |
Comment:
Variant classified as Uncertain Significance - Favor Benign. The p.Gly402Ala var iant in PCDH15 has been reported in the heterozygous state in 1 individual with … (more)
Variant classified as Uncertain Significance - Favor Benign. The p.Gly402Ala var iant in PCDH15 has been reported in the heterozygous state in 1 individual with hearing loss (Besnard 2014). It has also been identified in 0.26% (62/24036) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.br oadinstitute.org; dbSNP rs145017164). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic r ole. Computational prediction tools and conservation analysis do not provide str ong support for or against an impact to the protein. In summary, while the clini cal significance of the p.Gly402Ala variant is uncertain, its frequency suggests that it is more likely to be benign. ACMG/AMP Criteria applied: BS1_supporting. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Apr 27, 2017)
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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: SCV001259878.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(May 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 1F
Affected status: no
Allele origin:
germline
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Pars Genome Lab
Accession: SCV001736814.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
Sex: mixed
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Likely benign
(Nov 30, 2021)
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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: SCV001819602.3
First in ClinVar: Sep 08, 2021 Last updated: Mar 04, 2023 |
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Identified heterozygous in an individual with nonsyndromic hearing loss who also … (more)
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Identified heterozygous in an individual with nonsyndromic hearing loss who also harbored variants in two other hearing loss-associated genes (Besnard et al., 2014).; This variant is associated with the following publications: (PMID: 24498627) (less)
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Likely benign
(Jan 29, 2024)
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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: SCV001044828.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024 |
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Uncertain significance
(Jan 13, 2023)
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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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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004225243.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
BS1_supporting
Number of individuals with the variant: 1
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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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Experience of targeted Usher exome sequencing as a clinical test. | Besnard T | Molecular genetics & genomic medicine | 2014 | PMID: 24498627 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PCDH15 | - | - | - | - |
Text-mined citations for rs145017164 ...
HelpRecord last updated Feb 20, 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.