PP3, PM2
ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.2501T>A (p.Val834Asp)
Germline
Classification
Help
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.
(2)
Help
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
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000053.4(ATP7B):c.2501T>A (p.Val834Asp)
Variation ID: 2683231 Accession: VCV002683231.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q14.3 13: 51950346 (GRCh38) [ NCBI UCSC ] 13: 52524482 (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 Jan 6, 2024 Apr 20, 2024 Nov 20, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000053.4:c.2501T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Val834Asp missense NM_001005918.3:c.2015T>A NP_001005918.1:p.Val672Asp missense NM_001243182.2:c.2168T>A NP_001230111.1:p.Val723Asp missense NM_001330578.2:c.2267T>A NP_001317507.1:p.Val756Asp missense NM_001330579.2:c.2249T>A NP_001317508.1:p.Val750Asp missense NM_001406511.1:c.2501T>A NP_001393440.1:p.Val834Asp missense NM_001406512.1:c.2501T>A NP_001393441.1:p.Val834Asp missense NM_001406513.1:c.2501T>A NP_001393442.1:p.Val834Asp missense NM_001406514.1:c.2468T>A NP_001393443.1:p.Val823Asp missense NM_001406515.1:c.2501T>A NP_001393444.1:p.Val834Asp missense NM_001406516.1:c.2501T>A NP_001393445.1:p.Val834Asp missense NM_001406517.1:c.2405T>A NP_001393446.1:p.Val802Asp missense NM_001406518.1:c.2405T>A NP_001393447.1:p.Val802Asp missense NM_001406519.1:c.2501T>A NP_001393448.1:p.Val834Asp missense NM_001406520.1:c.2357T>A NP_001393449.1:p.Val786Asp missense NM_001406521.1:c.2357T>A NP_001393450.1:p.Val786Asp missense NM_001406522.1:c.2357T>A NP_001393451.1:p.Val786Asp missense NM_001406523.1:c.2501T>A NP_001393452.1:p.Val834Asp missense NM_001406524.1:c.2324T>A NP_001393453.1:p.Val775Asp missense NM_001406525.1:c.2501T>A NP_001393454.1:p.Val834Asp missense NM_001406526.1:c.2501T>A NP_001393455.1:p.Val834Asp missense NM_001406527.1:c.2267T>A NP_001393456.1:p.Val756Asp missense NM_001406528.1:c.2267T>A NP_001393457.1:p.Val756Asp missense NM_001406530.1:c.2261T>A NP_001393459.1:p.Val754Asp missense NM_001406531.1:c.2249T>A NP_001393460.1:p.Val750Asp missense NM_001406532.1:c.2249T>A NP_001393461.1:p.Val750Asp missense NM_001406534.1:c.2267T>A NP_001393463.1:p.Val756Asp missense NM_001406535.1:c.2501T>A NP_001393464.1:p.Val834Asp missense NM_001406536.1:c.2171T>A NP_001393465.1:p.Val724Asp missense NM_001406537.1:c.2357T>A NP_001393466.1:p.Val786Asp missense NM_001406538.1:c.2267T>A NP_001393467.1:p.Val756Asp missense NM_001406539.1:c.2072T>A NP_001393468.1:p.Val691Asp missense NM_001406540.1:c.2249T>A NP_001393469.1:p.Val750Asp missense NM_001406541.1:c.2015T>A NP_001393470.1:p.Val672Asp missense NM_001406542.1:c.2015T>A NP_001393471.1:p.Val672Asp missense NM_001406543.1:c.2153T>A NP_001393472.1:p.Val718Asp missense NM_001406544.1:c.1919T>A NP_001393473.1:p.Val640Asp missense NM_001406545.1:c.1853T>A NP_001393474.1:p.Val618Asp missense NM_001406546.1:c.2015T>A NP_001393475.1:p.Val672Asp missense NM_001406547.1:c.1853T>A NP_001393476.1:p.Val618Asp missense NM_001406548.1:c.1286-185T>A intron variant NC_000013.11:g.51950346A>T NC_000013.10:g.52524482A>T NG_008806.1:g.66149T>A - Protein change
- V618D, V640D, V672D, V691D, V718D, V723D, V724D, V750D, V754D, V756D, V775D, V786D, V802D, V823D, V834D
- Other names
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p.Val834Asp
- Canonical SPDI
- NC_000013.11:51950345:A:T
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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
Help
The frequency of the allele represented by this VCV record.
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- 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. |
|||
| ATP7B | - | - |
GRCh38 GRCh37 |
2918 | 3062 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
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Nov 28, 2022 | RCV003482098.1 | |
| Uncertain significance (1) |
criteria provided, single submitter
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Nov 20, 2023 | RCV004011338.2 |
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
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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|---|---|---|---|---|---|
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Uncertain significance
(Nov 28, 2022)
|
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: SCV004226446.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP3, PM2
Number of individuals with the variant: 1
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Uncertain Significance
(Nov 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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Wilson disease
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004840204.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This missense variant replaces valine with aspartic acid at codon 834 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact … (more)
This missense variant replaces valine with aspartic acid at codon 834 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant alters a conserved valine residue in the actuator domain of the ATP7B protein (a.a. 786 - 917), a highly conserved region that is considered to be important for ATP7B protein function (PMID: 35245129; ClinVar). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least one individual affected with Wilson disease (PMID: 36360177). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 1
|
Comment:
Comment:
This missense variant replaces valine with aspartic acid at codon 834 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant alters a conserved valine residue in the actuator domain of the ATP7B protein (a.a. 786 - 917), a highly conserved region that is considered to be important for ATP7B protein function (PMID: 35245129; ClinVar). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least one individual affected with Wilson disease (PMID: 36360177). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
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. |
Comment:
PP3, PM2
Comment:
This missense variant replaces valine with aspartic acid at codon 834 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant alters a conserved valine residue in the actuator domain of the ATP7B protein (a.a. 786 - 917), a highly conserved region that is considered to be important for ATP7B protein function (PMID: 35245129; ClinVar). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least one individual affected with Wilson disease (PMID: 36360177). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Design, Optimization and Validation of the ARMS PCR Protocol for the Rapid Diagnosis of Wilson's Disease Using a Panel of 14 Common Mutations for the European Population. | Garbuz MM | Genes | 2022 | PMID: 36360177 |
| Structure of the Wilson disease copper transporter ATP7B. | Bitter RM | Science advances | 2022 | PMID: 35245129 |
Text-mined citations for this variant ...
HelpRecord last updated May 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.