The frameshift c.727_728insA p.Phe243TyrfsTer2 variant in the ATP7B gene gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is novel not in any individuals in gnomAD Exomes and 1000 Genomes. This variant causes a frameshift starting with codon Phenylalanine 243, changes this amino acid to Tyrosine residue, and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Phe243TyrfsTer2. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.727_728insA (p.Phe243fs)
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.
(1)
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.
Likely pathogenic
1
criteria provided, single submitter
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.727_728insA (p.Phe243fs)
Variation ID: 3236436 Accession: VCV003236436.2
- Type and length
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Insertion, 1 bp
- Location
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Cytogenetic: 13q14.3 13: 51974492-51974493 (GRCh38) [ NCBI UCSC ] 13: 52548628-52548629 (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 May 27, 2024 Jun 17, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000053.4:c.727_728insA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Phe243fs frameshift NM_001005918.3:c.727_728insA NP_001005918.1:p.Phe243fs frameshift NM_001243182.2:c.727_728insA NP_001230111.1:p.Phe243fs frameshift NM_001330578.2:c.727_728insA NP_001317507.1:p.Phe243fs frameshift NM_001330579.2:c.727_728insA NP_001317508.1:p.Phe243fs frameshift NM_001406511.1:c.727_728insA NP_001393440.1:p.Phe243fs frameshift NM_001406512.1:c.727_728insA NP_001393441.1:p.Phe243fs frameshift NM_001406513.1:c.727_728insA NP_001393442.1:p.Phe243fs frameshift NM_001406514.1:c.727_728insA NP_001393443.1:p.Phe243fs frameshift NM_001406515.1:c.727_728insA NP_001393444.1:p.Phe243fs frameshift NM_001406516.1:c.727_728insA NP_001393445.1:p.Phe243fs frameshift NM_001406517.1:c.631_632insA NP_001393446.1:p.Phe211fs frameshift NM_001406518.1:c.631_632insA NP_001393447.1:p.Phe211fs frameshift NM_001406519.1:c.727_728insA NP_001393448.1:p.Phe243fs frameshift NM_001406520.1:c.727_728insA NP_001393449.1:p.Phe243fs frameshift NM_001406521.1:c.727_728insA NP_001393450.1:p.Phe243fs frameshift NM_001406522.1:c.727_728insA NP_001393451.1:p.Phe243fs frameshift NM_001406523.1:c.727_728insA NP_001393452.1:p.Phe243fs frameshift NM_001406524.1:c.727_728insA NP_001393453.1:p.Phe243fs frameshift NM_001406525.1:c.727_728insA NP_001393454.1:p.Phe243fs frameshift NM_001406526.1:c.727_728insA NP_001393455.1:p.Phe243fs frameshift NM_001406527.1:c.727_728insA NP_001393456.1:p.Phe243fs frameshift NM_001406528.1:c.727_728insA NP_001393457.1:p.Phe243fs frameshift NM_001406530.1:c.631_632insA NP_001393459.1:p.Phe211fs frameshift NM_001406531.1:c.727_728insA NP_001393460.1:p.Phe243fs frameshift NM_001406532.1:c.727_728insA NP_001393461.1:p.Phe243fs frameshift NM_001406534.1:c.727_728insA NP_001393463.1:p.Phe243fs frameshift NM_001406535.1:c.727_728insA NP_001393464.1:p.Phe243fs frameshift NM_001406536.1:c.631_632insA NP_001393465.1:p.Phe211fs frameshift NM_001406537.1:c.727_728insA NP_001393466.1:p.Phe243fs frameshift NM_001406538.1:c.727_728insA NP_001393467.1:p.Phe243fs frameshift NM_001406539.1:c.631_632insA NP_001393468.1:p.Phe211fs frameshift NM_001406540.1:c.727_728insA NP_001393469.1:p.Phe243fs frameshift NM_001406541.1:c.727_728insA NP_001393470.1:p.Phe243fs frameshift NM_001406542.1:c.727_728insA NP_001393471.1:p.Phe243fs frameshift NM_001406543.1:c.631_632insA NP_001393472.1:p.Phe211fs frameshift NM_001406544.1:c.631_632insA NP_001393473.1:p.Phe211fs frameshift NM_001406545.1:c.727_728insA NP_001393474.1:p.Phe243fs frameshift NM_001406546.1:c.727_728insA NP_001393475.1:p.Phe243fs frameshift NM_001406547.1:c.727_728insA NP_001393476.1:p.Phe243fs frameshift NM_001406548.1:c.727_728insA NP_001393477.1:p.Phe243fs frameshift NC_000013.11:g.51974492_51974493insT NC_000013.10:g.52548628_52548629insT NG_008806.1:g.42002_42003insA - Protein change
- F211fs, F243fs
- Other names
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- Canonical SPDI
- NC_000013.11:51974492::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. |
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| 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. |
|---|---|---|---|---|
| Likely pathogenic (1) |
criteria provided, single submitter
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- | RCV004555804.2 |
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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Likely pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
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Wilson disease
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV005044812.2
First in ClinVar: May 26, 2024 Last updated: Jun 17, 2024 |
Comment:
The frameshift c.727_728insA p.Phe243TyrfsTer2 variant in the ATP7B gene gene has not been reported previously as a pathogenic variant nor as a benign variant, to … (more)
The frameshift c.727_728insA p.Phe243TyrfsTer2 variant in the ATP7B gene gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is novel not in any individuals in gnomAD Exomes and 1000 Genomes. This variant causes a frameshift starting with codon Phenylalanine 243, changes this amino acid to Tyrosine residue, and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Phe243TyrfsTer2. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic. (less)
|
Comment:
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:
The frameshift c.727_728insA p.Phe243TyrfsTer2 variant in the ATP7B gene gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is novel not in any individuals in gnomAD Exomes and 1000 Genomes. This variant causes a frameshift starting with codon Phenylalanine 243, changes this amino acid to Tyrosine residue, and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Phe243TyrfsTer2. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Jun 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.