ClinVar Genomic variation as it relates to human health
NM_002437.5(MPV17):c.280-1dup
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.
Pathogenic(9); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_002437.5(MPV17):c.280-1dup
Variation ID: 290443 Accession: VCV000290443.20
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 2p23.3 2: 27312584-27312585 (GRCh38) [ NCBI UCSC ] 2: 27535451-27535452 (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 Dec 6, 2016 Jun 17, 2024 Mar 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002437.5:c.280-1dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_002437.5:c.284dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_002437.5:c.284dupG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_002437.4:c.284dup NC_000002.12:g.27312590dup NC_000002.11:g.27535457dup NG_008075.1:g.14980dup NG_033055.1:g.679dup - Protein change
- Other names
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- Canonical SPDI
- NC_000002.12:27312584:CCCCCC:CCCCCCC
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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
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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MPV17 | - | - |
GRCh38 GRCh37 |
318 | 348 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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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Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
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Mar 29, 2024 | RCV000265576.7 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Sep 15, 2023 | RCV000486235.15 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 28, 2024 | RCV003469248.2 |
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
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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
(Jun 15, 2015)
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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: SCV000565695.3
First in ClinVar: Apr 27, 2017 Last updated: Apr 27, 2017 |
Comment:
The c.284dupG variant ispredicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although this duplication has not been … (more)
The c.284dupG variant ispredicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although this duplication has not been previously reported to our knowledge, itis expected to be a pathogenic variant. (less)
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Pathogenic
(Dec 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial DNA depletion syndrome 6
Affected status: yes
Allele origin:
germline
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Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
Accession: SCV000746014.1
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Pathogenic
(Aug 16, 2016)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000345002.3
First in ClinVar: Dec 06, 2016 Last updated: Jul 31, 2019 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Mar 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002318580.1
First in ClinVar: Apr 02, 2022 Last updated: Apr 02, 2022 |
Comment:
Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported … (more)
Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000290443, PMID:27848944). The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency:0.0000198). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Failure to thrive (present) , Hepatomegaly (present) , Jaundice (present)
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Pathogenic
(Apr 16, 2021)
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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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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV002520078.1
First in ClinVar: May 27, 2022 Last updated: May 27, 2022 |
Comment:
PVS1, PS4_moderate, PM2, PM3
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Pathogenic
(Jul 18, 2022)
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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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Revvity Omics, Revvity
Accession: SCV003819652.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Sep 15, 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: SCV001585137.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Phe96Leufs*17) in the MPV17 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Phe96Leufs*17) in the MPV17 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MPV17 are known to be pathogenic (PMID: 23714749). This variant is present in population databases (rs766160589, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with clinical features of mitochondrial DNA maintenance defect (PMID: 27848944, 29282788). ClinVar contains an entry for this variant (Variation ID: 290443). For these reasons, this variant has been classified as Pathogenic. (less)
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Uncertain significance
(Mar 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004807597.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV005042971.1
First in ClinVar: May 12, 2024 Last updated: May 12, 2024 |
Comment:
The frameshift c.284dupp.Phe96LeufsTer17 variant in MPV17 gene has been reported previously in homozygous or compound heterozygous state in individuals affected with mitochondrial DNA maintenance defect … (more)
The frameshift c.284dupp.Phe96LeufsTer17 variant in MPV17 gene has been reported previously in homozygous or compound heterozygous state in individuals affected with mitochondrial DNA maintenance defect El-Hattab et al., 2018. This variant is reported with the allele frequency of 0.002% in the gnomAD Exomes and novel in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic by multiple submitters. This variant causes a frameshift starting with codon Phenylalanine 96, changes this amino acid to Leucine residue, and creates a premature Stop codon at position 17 of the new reading frame, denoted p.Phe96LeufsTer17. This variant is predicted to cause loss of normal protein function through protein truncation. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MPV17 are known to be pathogenic Uusimaa et al., 2014. For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Abnormality of the nervous system (present)
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Pathogenic
(Mar 28, 2024)
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criteria provided, single submitter
Method: clinical testing
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Charcot-Marie-Tooth disease, axonal, type 2EE
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004193762.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Navajo neurohepatopathy
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001462525.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 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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Diagnostic power and clinical impact of exome sequencing in a cohort of 500 patients with rare diseases. | Quaio CRDC | American journal of medical genetics. Part C, Seminars in medical genetics | 2020 | PMID: 33258288 |
MPV17-related mitochondrial DNA maintenance defect: New cases and review of clinical, biochemical, and molecular aspects. | El-Hattab AW | Human mutation | 2018 | PMID: 29282788 |
Clinical exome sequencing: results from 2819 samples reflecting 1000 families. | Trujillano D | European journal of human genetics : EJHG | 2017 | PMID: 27848944 |
Clinical, biochemical, cellular and molecular characterization of mitochondrial DNA depletion syndrome due to novel mutations in the MPV17 gene. | Uusimaa J | European journal of human genetics : EJHG | 2014 | PMID: 23714749 |
Text-mined citations for rs766160589 ...
HelpRecord last updated Aug 04, 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.