ClinVar Genomic variation as it relates to human health
NM_001384140.1(PCDH15):c.1863_1864dup (p.Ser622fs)
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
-
NM_001384140.1(PCDH15):c.1863_1864dup (p.Ser622fs)
Variation ID: 2136864 Accession: VCV002136864.3
- Type and length
-
Microsatellite, 2 bp
- Location
-
Cytogenetic: 10q21.1 10: 55892687-55892688 (GRCh37) [ NCBI UCSC ] 10: 54132927-54132928 (GRCh38) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Feb 8, 2023 Feb 14, 2024 Jun 19, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001384140.1:c.1863_1864dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001371069.1:p.Ser622fs frameshift NM_033056.4:c.1863_1864dup MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_149045.3:p.Ser622fs frameshift NM_001142763.2:c.1878_1879dup NP_001136235.1:p.Ser627fs frameshift NM_001142764.2:c.1863_1864dup NP_001136236.1:p.Ser622fs frameshift NM_001142765.2:c.1784+20169TA[3] intron variant NM_001142766.2:c.1863_1864dup NP_001136238.1:p.Ser622fs frameshift NM_001142767.2:c.1752_1753dup NP_001136239.1:p.Ser585fs frameshift NM_001142768.2:c.1797_1798dup NP_001136240.1:p.Ser600fs frameshift NM_001142769.3:c.1899_1900dup NP_001136241.1:p.Ser634fs frameshift NM_001142770.3:c.1863_1864dup NP_001136242.1:p.Ser622fs frameshift NM_001142771.2:c.1878_1879dup NP_001136243.1:p.Ser627fs frameshift NM_001142772.2:c.1863_1864dup NP_001136244.1:p.Ser622fs frameshift NM_001142773.2:c.1797_1798dup NP_001136245.1:p.Ser600fs frameshift NM_001354404.2:c.1797_1798dup NP_001341333.1:p.Ser600fs frameshift NM_001354411.2:c.1884_1885dup NP_001341340.1:p.Ser629fs frameshift NM_001354420.2:c.1863_1864dup NP_001341349.1:p.Ser622fs frameshift NM_001354429.2:c.1863_1864dup NP_001341358.1:p.Ser622fs frameshift NM_001354430.2:c.1863_1864dup NP_001341359.1:p.Ser622fs frameshift NC_000010.11:g.54132928TA[3] NC_000010.10:g.55892688TA[3] NG_009191.3:g.1501252TA[3] - Protein change
- S585fs, S634fs, S600fs, S622fs, S627fs, S629fs
- Other names
- NM_001384140.1:c.1863_1864dup
- Canonical SPDI
- NC_000010.11:54132927:TATA:TATATA
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
- Links
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 | ||
---|---|---|---|---|---|---|
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. |
|||
PCDH15 | - | - |
GRCh38 GRCh37 |
3320 | 3407 |
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. |
---|---|---|---|---|
Pathogenic (1) |
criteria provided, single submitter
|
Jun 19, 2023 | RCV003062260.2 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jan 24, 2023 | RCV003062261.2 | |
Pathogenic (1) |
criteria provided, single submitter
|
May 12, 2023 | RCV003475489.1 |
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. |
|
---|---|---|---|---|---|
Pathogenic
(Jan 24, 2023)
|
criteria provided, single submitter
Method: curation
|
Usher syndrome type 1F
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV003761071.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
The p.Ser622fs variant in PCDH15 has been reported in 3 individuals with Usher syndrome type 1F (PMID: 26166082, 30029497, 33724713) and has been identified in … (more)
The p.Ser622fs variant in PCDH15 has been reported in 3 individuals with Usher syndrome type 1F (PMID: 26166082, 30029497, 33724713) and has been identified in 0.005% (1/18338) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs764292129). 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. Of the 3 affected individuals, 2 of those were homozygotes, which increases the likelihood that the p.Ser622fs variant is pathogenic (PMID: 26166082, 30029497). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 622 and leads to a premature termination codon 9 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the PCDH15 gene is an established disease mechanism in autosomal recessive Usher syndrome type 1F. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Usher syndrome type 1F. ACMG/AMP Criteria applied: PVS1, PM2_supporting, PM3 (Richards 2015). (less)
|
|
Pathogenic
(May 12, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive nonsyndromic hearing loss 23
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004200826.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
Pathogenic
(Jun 19, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV003441641.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with PCDH15-related conditions (PMID: 26166082, … (more)
For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with PCDH15-related conditions (PMID: 26166082, 30029497). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser622Ilefs*9) in the PCDH15 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCDH15 are known to be pathogenic (PMID: 11398101, 11487575, 14570705). (less)
|
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 |
---|---|---|---|---|
Application of Whole Exome and Targeted Panel Sequencing in the Clinical Molecular Diagnosis of 319 Chinese Families with Inherited Retinal Dystrophy and Comparison Study. | Wang L | Genes | 2018 | PMID: 30029497 |
Identifying Children With Poor Cochlear Implantation Outcomes Using Massively Parallel Sequencing. | Wu CC | Medicine | 2015 | PMID: 26166082 |
PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23. | Ahmed ZM | Human molecular genetics | 2003 | PMID: 14570705 |
Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F. | Alagramam KN | Human molecular genetics | 2001 | PMID: 11487575 |
Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F. | Ahmed ZM | American journal of human genetics | 2001 | PMID: 11398101 |
Text-mined citations for this variant ...
HelpRecord last updated Mar 30, 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.