ClinVar Genomic variation as it relates to human health
NM_001378687.1(ATP2C1):c.2375_2378del (p.Phe792fs)
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_001378687.1(ATP2C1):c.2375_2378del (p.Phe792fs)
Variation ID: 372308 Accession: VCV000372308.9
- Type and length
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Microsatellite, 4 bp
- Location
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Cytogenetic: 3q22.1 3: 130997732-130997735 (GRCh38) [ NCBI UCSC ] 3: 130716576-130716579 (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 Mar 10, 2024 Mar 14, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001378687.1:c.2375_2378del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001365616.1:p.Phe792fs frameshift NM_001001485.3:c.2375_2378del NP_001001485.1:p.Phe792fs frameshift NM_001001486.2:c.2375_2378del NP_001001486.1:p.Phe792fs frameshift NM_001001487.2:c.2375_2378del NP_001001487.1:p.Phe792fs frameshift NM_001199179.3:c.2375_2378del NP_001186108.1:p.Phe792fs frameshift NM_001199180.2:c.2477_2480del NP_001186109.1:p.Phe826fs frameshift NM_001199181.3:c.2477_2480del NP_001186110.1:p.Phe826fs frameshift NM_001199182.2:c.2360_2363del NP_001186111.1:p.Phe787fs frameshift NM_001199183.2:c.2327_2330del NP_001186112.1:p.Phe776fs frameshift NM_001199184.3:c.2327_2330del NP_001186113.1:p.Phe776fs frameshift NM_001199185.2:c.2375_2378del NP_001186114.1:p.Phe792fs frameshift NM_001378511.1:c.2477_2480del NP_001365440.1:p.Phe826fs frameshift NM_001378512.1:c.2375_2378del NP_001365441.1:p.Phe792fs frameshift NM_001378513.1:c.2375_2378del NP_001365442.1:p.Phe792fs frameshift NM_001378514.1:c.2327_2330del NP_001365443.1:p.Phe776fs frameshift NM_014382.4:c.2375_2378del NM_014382.5:c.2375_2378del NP_055197.2:p.Phe792fs frameshift NC_000003.12:g.130997733TTGT[1] NC_000003.11:g.130716577TTGT[1] NG_007379.2:g.152209TTGT[1] - Protein change
- F787fs, F776fs, F792fs, F826fs
- Other names
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- Canonical SPDI
- NC_000003.12:130997731:TTTGTTTGT:TTTGT
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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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ATP2C1 | - | - |
GRCh38 GRCh37 |
213 | 237 |
Conditions - Germline
Condition
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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
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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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Pathogenic (2) |
criteria provided, single submitter
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Dec 20, 2021 | RCV000005926.11 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Mar 14, 2023 | RCV000412997.4 |
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
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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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Pathogenic
(Dec 21, 2016)
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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: SCV000490418.1
First in ClinVar: Jan 09, 2017 Last updated: Jan 09, 2017 |
Comment:
The c.2375_2378delTTGT variant in the ATP2C1 gene has been reported previously in association with Hailey-Hailey disease (Hu et al., 2000). The deletion causes a frameshift … (more)
The c.2375_2378delTTGT variant in the ATP2C1 gene has been reported previously in association with Hailey-Hailey disease (Hu et al., 2000). The deletion causes a frameshift starting with codon Phenylalanine 792, changes this amino acid to a Serine residue and creates a premature Stop codon at position 10 of the new reading frame, denoted p.Phe792SerfsX10. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, we interpret this variant as pathogenic. (less)
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Pathogenic
(Dec 20, 2021)
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criteria provided, single submitter
Method: clinical testing
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Familial benign pemphigus
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003811156.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Mar 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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Invitae
Accession: SCV002241210.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 372308). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 372308). This premature translational stop signal has been observed in individual(s) with Hailey-Hailey disease (PMID: 10615129, 25837627, 28035777, 29944739). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe792Serfs*10) in the ATP2C1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP2C1 are known to be pathogenic (PMID: 10615129, 10767338, 11841554). (less)
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Pathogenic
(Jan 01, 2000)
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no assertion criteria provided
Method: literature only
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HAILEY-HAILEY DISEASE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000026108.4
First in ClinVar: Apr 04, 2013 Last updated: Mar 10, 2024 |
Comment on evidence:
In 2 unrelated families with Hailey-Hailey disease (HHD; 169600), Hu et al. (2000) found an identical 4-bp deletion of 2374delTTTG in the ATP2C1 gene. The … (more)
In 2 unrelated families with Hailey-Hailey disease (HHD; 169600), Hu et al. (2000) found an identical 4-bp deletion of 2374delTTTG in the ATP2C1 gene. The 2 families had different alleles of the D3S1587 marker, a locus less than 100 kb from the mutant gene, on the mutant chromosome. This may indicate that these were independent mutations. The deletion resulted in a premature termination codon 10 amino acids downstream of the mutation. (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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Identification of a recurrent mutation in ATP2C1 demonstrates that papular acantholytic dyskeratosis and Hailey-Hailey disease are allelic disorders. | Vodo D | The British journal of dermatology | 2018 | PMID: 29944739 |
Mendelian Disorders of Cornification Caused by Defects in Intracellular Calcium Pumps: Mutation Update and Database for Variants in ATP2A2 and ATP2C1 Associated with Darier Disease and Hailey-Hailey Disease. | Nellen RG | Human mutation | 2017 | PMID: 28035777 |
A family with atypical Hailey Hailey disease--is there more to the underlying genetics than ATP2C1? | van Beek N | PloS one | 2015 | PMID: 25837627 |
Hailey-Hailey disease: molecular and clinical characterization of novel mutations in the ATP2C1 gene. | Dobson-Stone C | The Journal of investigative dermatology | 2002 | PMID: 11841554 |
Hailey-Hailey disease is caused by mutations in ATP2C1 encoding a novel Ca(2+) pump. | Sudbrak R | Human molecular genetics | 2000 | PMID: 10767338 |
Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease. | Hu Z | Nature genetics | 2000 | PMID: 10615129 |
Text-mined citations for rs1057517706 ...
HelpRecord last updated Mar 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.