ClinVar Genomic variation as it relates to human health
NM_002437.5(MPV17):c.376-9T>G
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(3); Likely pathogenic(3); 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.376-9T>G
Variation ID: 593343 Accession: VCV000593343.17
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p23.3 2: 27312255 (GRCh38) [ NCBI UCSC ] 2: 27535123 (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 16, 2018 Feb 20, 2024 Dec 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002437.5:c.376-9T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NC_000002.12:g.27312255A>C NC_000002.11:g.27535123A>C NG_008075.1:g.15309T>G NG_033055.1:g.1008T>G - Protein change
- Other names
- IVS5, T-G, -9
- Canonical SPDI
- NC_000002.12:27312254:A:C
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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.
The Genome Aggregation Database (gnomAD), exomes 0.00001
The Genome Aggregation Database (gnomAD) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
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
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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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MPV17 | - | - |
GRCh38 GRCh37 |
312 | 342 | |
TRIM54 | - | - |
GRCh38 GRCh37 |
33 | 52 | |
UCN | - | - |
GRCh38 GRCh37 |
9 | 28 |
Conditions - Germline
Condition
Help
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
Help
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 (2) |
criteria provided, conflicting classifications
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Dec 10, 2023 | RCV000728355.8 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Sep 5, 2018 | RCV000735227.2 | |
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Nov 10, 2023 | RCV000768422.11 |
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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Uncertain significance
(Jul 20, 2017)
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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: SCV000855914.1
First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Likely pathogenic
(Sep 05, 2018)
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criteria provided, single submitter
Method: clinical testing
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MPV17-related mitochondrial DNA maintenance defect
The phenotype in OMIM is limited to
(more...)
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
paternal
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Undiagnosed Diseases Network, NIH
Accession: SCV000863436.1
First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018 |
Comment:
RNA sequencing showed change in splicing
Number of individuals with the variant: 1
Clinical Features:
Tinnitus (present) , Steppage gait (present) , Skeletal muscle atrophy (present) , Sensory neuropathy (present) , Sensory impairment (present) , Sensorimotor neuropathy (present) , Scoliosis … (more)
Tinnitus (present) , Steppage gait (present) , Skeletal muscle atrophy (present) , Sensory neuropathy (present) , Sensory impairment (present) , Sensorimotor neuropathy (present) , Scoliosis (present) , Ptosis (present) , Progressive muscle weakness (present) , Photophobia (present) , Peripheral demyelination (present) , Muscle weakness (present) , Muscle cramps (present) , Migraine (present) , Limb pain (present) , Impaired vibratory sensation (present) , Impaired proprioception (present) , Headache (present) , Gait imbalance (present) , Distal upper limb muscle weakness (present) , Distal lower limb muscle weakness (present) , Distal lower limb amyotrophy (present) , Difficulty walking (present) , Difficulty standing (present) , Broad-based gait (present) , Areflexia (present) , Anisocoria (present) (less)
Age: 30-39 years
Sex: female
Ethnicity/Population group: Iranian
Tissue: blood
Testing laboratory: HudsonAlpha Clinical Services Lab, LLC,HudsonAlpha Clinical Services Lab, LLC
Date variant was reported to submitter: 2018-07-15
Testing laboratory interpretation: Uncertain significance
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Pathogenic
(Oct 24, 2019)
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criteria provided, single submitter
Method: clinical testing
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Charcot-Marie-Tooth disease, axonal, type 2EE
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV001149840.1
First in ClinVar: Feb 03, 2020 Last updated: Feb 03, 2020 |
Sex: male
Tissue: blood
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Likely pathogenic
(Jan 01, 2019)
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criteria provided, single submitter
Method: clinical testing
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Charcot-Marie-Tooth disease, axonal, type 2EE
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001439924.1
First in ClinVar: Oct 31, 2020 Last updated: Oct 31, 2020 |
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Pathogenic
(Nov 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Charcot-Marie-Tooth disease, axonal, type 2EE
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV004101662.1
First in ClinVar: Nov 11, 2023 Last updated: Nov 11, 2023 |
Clinical Features:
Polyneuropathy (present) , Areflexia (present) , Impaired vibration sensation in the lower limbs (present) , Steppage gait (present) , Sensory ataxic neuropathy (present) , EMG: … (more)
Polyneuropathy (present) , Areflexia (present) , Impaired vibration sensation in the lower limbs (present) , Steppage gait (present) , Sensory ataxic neuropathy (present) , EMG: chronic denervation signs (present) , Peripheral axonal neuropathy (present) , Distal lower limb muscle weakness (present) (less)
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Likely pathogenic
(Oct 22, 2023)
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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: SCV004193734.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Dec 10, 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: SCV002131199.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 20, 2024 |
Comment:
This sequence change falls in intron 5 of the MPV17 gene. It does not directly change the encoded amino acid sequence of the MPV17 protein. … (more)
This sequence change falls in intron 5 of the MPV17 gene. It does not directly change the encoded amino acid sequence of the MPV17 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs368900406, gnomAD 0.003%). This variant has been observed in individual(s) with peripheral sensorimotor neuropathy (PMID: 30298599). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 593343). Studies have shown that this variant results in skipping of exon 6, but is expected to preserve the integrity of the reading-frame (PMID: 30298599). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Apr 29, 2019)
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no assertion criteria provided
Method: literature only
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CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2EE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000899174.2
First in ClinVar: Apr 29, 2019 Last updated: May 02, 2019 |
Comment on evidence:
In 3 brothers from the religious minority of 'Jesidians' (Yazidis) in northern Iraq with autosomal recessive Charcot-Marie-Tooth neuropathy type 2EE (CMT2EE; 618400), Baumann et al. … (more)
In 3 brothers from the religious minority of 'Jesidians' (Yazidis) in northern Iraq with autosomal recessive Charcot-Marie-Tooth neuropathy type 2EE (CMT2EE; 618400), Baumann et al. (2019) identified a homozygous T-to-G transversion in intron 5 of the MPV17 gene (c.376-9T-G), resulting in a splicing defect. RT-PCR analysis of patient cells showed that the mutation resulted in skipping of exon 6 in the majority of mRNAs, causing an in-frame deletion of 11 residues (Asp126_Tyr136del). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was found at a low frequency in the gnomAD database. (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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MPV17 mutations in juvenile- and adult-onset axonal sensorimotor polyneuropathy. | Baumann M | Clinical genetics | 2019 | PMID: 30298599 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MPV17 | - | - | - | - |
Text-mined citations for rs368900406 ...
HelpRecord last updated Apr 20, 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.