ClinVar Genomic variation as it relates to human health
NM_001384140.1(PCDH15):c.2435T>C (p.Ile812Thr)
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.2435T>C (p.Ile812Thr)
Variation ID: 178628 Accession: VCV000178628.37
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q21.1 10: 54022983 (GRCh38) [ NCBI UCSC ] 10: 55782743 (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 28, 2015 Oct 8, 2024 May 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001384140.1:c.2435T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001371069.1:p.Ile812Thr missense NM_033056.4:c.2435T>C MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_149045.3:p.Ile812Thr missense NM_001142763.2:c.2450T>C NP_001136235.1:p.Ile817Thr missense NM_001142764.2:c.2435T>C NP_001136236.1:p.Ile812Thr missense NM_001142765.2:c.2222T>C NP_001136237.1:p.Ile741Thr missense NM_001142766.2:c.2435T>C NP_001136238.1:p.Ile812Thr missense NM_001142767.2:c.2324T>C NP_001136239.1:p.Ile775Thr missense NM_001142768.2:c.2369T>C NP_001136240.1:p.Ile790Thr missense NM_001142769.3:c.2471T>C NP_001136241.1:p.Ile824Thr missense NM_001142770.3:c.2435T>C NP_001136242.1:p.Ile812Thr missense NM_001142771.2:c.2450T>C NP_001136243.1:p.Ile817Thr missense NM_001142772.2:c.2435T>C NP_001136244.1:p.Ile812Thr missense NM_001142773.2:c.2369T>C NP_001136245.1:p.Ile790Thr missense NM_001354404.2:c.2369T>C NP_001341333.1:p.Ile790Thr missense NM_001354411.2:c.2456T>C NP_001341340.1:p.Ile819Thr missense NM_001354420.2:c.2435T>C NP_001341349.1:p.Ile812Thr missense NM_001354429.2:c.2435T>C NP_001341358.1:p.Ile812Thr missense NM_001354430.2:c.2435T>C NP_001341359.1:p.Ile812Thr missense NC_000010.11:g.54022983A>G NC_000010.10:g.55782743A>G NG_009191.3:g.1611200T>C - Protein change
- I812T, I775T, I817T, I824T, I741T, I790T, I819T
- Other names
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- Canonical SPDI
- NC_000010.11:54022982:A: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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0.00399 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00070
Exome Aggregation Consortium (ExAC) 0.00090
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00284
The Genome Aggregation Database (gnomAD) 0.00325
Trans-Omics for Precision Medicine (TOPMed) 0.00356
1000 Genomes Project 0.00399
1000 Genomes Project 30x 0.00406
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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PCDH15 | - | - |
GRCh38 GRCh37 |
3391 | 3481 |
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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Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Jul 12, 2022 | RCV000155383.10 | |
Benign/Likely benign (8) |
criteria provided, multiple submitters, no conflicts
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May 1, 2024 | RCV000513885.26 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 9, 2017 | RCV000664808.1 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV001104967.4 |
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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Benign
(Oct 14, 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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000885888.2
First in ClinVar: Nov 05, 2017 Last updated: Feb 20, 2024 |
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Benign
(Dec 19, 2014)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000226971.5
First in ClinVar: Jun 28, 2015 Last updated: May 03, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Likely benign
(-)
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criteria provided, single submitter
Method: not provided
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005220770.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
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Likely benign
(Apr 11, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000610806.1
First in ClinVar: Nov 05, 2017 Last updated: Nov 05, 2017 |
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Likely benign
(Jan 09, 2017)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 1F
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000788823.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Likely benign
(May 07, 2012)
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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: SCV000205070.5
First in ClinVar: Jan 31, 2015 Last updated: May 03, 2018 |
Comment:
Ile812Thr in Exon 19 of PCDH15: This variant is not expected to have clinical si gnificance because it has been identified in 0.7% (26/3738) of … (more)
Ile812Thr in Exon 19 of PCDH15: This variant is not expected to have clinical si gnificance because it has been identified in 0.7% (26/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs61731363). (less)
Number of individuals with the variant: 4
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Likely benign
(Apr 17, 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: SCV001803026.1
First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 27766948)
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Benign
(Jan 30, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001109075.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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Likely benign
(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: SCV001261876.1
First in ClinVar: May 31, 2020 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
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Benign
(Jul 12, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002570971.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
Variant summary: PCDH15 c.2435T>C (p.Ile812Thr) results in a non-conservative amino acid change located in the Cadherin-like domain (IPR002126) of the encoded protein sequence. Four of … (more)
Variant summary: PCDH15 c.2435T>C (p.Ile812Thr) results in a non-conservative amino acid change located in the Cadherin-like domain (IPR002126) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0031 in 152112 control chromosomes, predominantly at a frequency of 0.011 within the African or African-American subpopulation in the gnomAD v3 database (genomes data), including 2 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 3.5 fold of the estimated maximal expected allele frequency for a pathogenic variant in PCDH15 causing Usher Syndrome Type 1F phenotype (0.0032), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Six ClinVar submitters (evaluation after 2014) cite the variant as likely benign (n=4) and benign (n=2). Based on the evidence outlined above, the variant was classified as benign. (less)
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Likely benign
(May 01, 2024)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV005051408.4
First in ClinVar: Jun 17, 2024 Last updated: Oct 08, 2024 |
Comment:
PCDH15: BS1
Number of individuals with the variant: 1
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001978985.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001979962.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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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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Utilization of amplicon-based targeted sequencing panel for the massively parallel sequencing of sporadic hearing impairment patients from Saudi Arabia. | Dallol A | BMC medical genetics | 2016 | PMID: 27766948 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PCDH15 | - | - | - | - |
Text-mined citations for rs61731363 ...
HelpRecord last updated Oct 08, 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.