ClinVar Genomic variation as it relates to human health
NM_005797.4(MPZL2):c.220C>T (p.Gln74Ter)
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_005797.4(MPZL2):c.220C>T (p.Gln74Ter)
Variation ID: 585269 Accession: VCV000585269.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q23.3 11: 118262936 (GRCh38) [ NCBI UCSC ] 11: 118133651 (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 Feb 25, 2019 Sep 3, 2023 Dec 13, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_005797.4:c.220C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005788.1:p.Gln74Ter nonsense NM_144765.3:c.220C>T NP_658911.1:p.Gln74Ter nonsense NC_000011.10:g.118262936G>A NC_000011.9:g.118133651G>A - Protein change
- Q74*
- Other names
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- Canonical SPDI
- NC_000011.10:118262935:G:A
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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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0.00140 (A)
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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00024
The Genome Aggregation Database (gnomAD), exomes 0.00041
1000 Genomes Project 30x 0.00109
1000 Genomes Project 0.00140
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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MPZL2 | - | - |
GRCh38 GRCh37 |
36 | 67 |
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
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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Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Dec 13, 2022 | RCV000710019.11 | |
Likely pathogenic (1) |
no assertion criteria provided
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Apr 12, 2018 | RCV003325308.2 |
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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Pathogenic
(May 13, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hearing loss, autosomal recessive 111
Affected status: yes
Allele origin:
germline
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Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University
Accession: SCV001622422.1
First in ClinVar: May 20, 2021 Last updated: May 20, 2021 |
Clinical Features:
Global developmental delay (present) , Intellectual disability (present) , Childhood-onset truncal obesity (present) , Motor delay (present) , Hearing abnormality (present)
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Pathogenic
(Jan 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hearing loss, autosomal recessive 111
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002058530.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are … (more)
Stop-gained (nonsense): 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 (PVS1_VS).The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000585269, PMID:29961571, 3billion dataset). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000397, PM2_M). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (3billion dataset, PM3_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Hearing impairment (present)
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Pathogenic
(Dec 13, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hearing loss, autosomal recessive 111
Affected status: yes
Allele origin:
biparental
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Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital
Accession: SCV002762662.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
Number of individuals with the variant: 17
Age: 5-21 years
Sex: mixed
Ethnicity/Population group: Han Chinese
Geographic origin: China
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Pathogenic
(Feb 22, 2019)
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no assertion criteria provided
Method: literature only
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DEAFNESS, AUTOSOMAL RECESSIVE 111
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000840384.2
First in ClinVar: Oct 19, 2018 Last updated: Feb 25, 2019 |
Comment on evidence:
For discussion of the c.220C-T transition (c.220C-T, NM_005797.3) in the MPZL2 gene, resulting in a gln74-to-ter (Q74X) substitution, that was found in compound heterozygous state … (more)
For discussion of the c.220C-T transition (c.220C-T, NM_005797.3) in the MPZL2 gene, resulting in a gln74-to-ter (Q74X) substitution, that was found in compound heterozygous state in Turkish patients with autosomal recessive deafness-111 by Wesdorp et al. (2018), see 604873.0001. (less)
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Pathogenic
(Aug 28, 2019)
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no assertion criteria provided
Method: research
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Hearing loss, autosomal recessive 111
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Laboratory of Molecular Genetics, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine
Accession: SCV000986688.1
First in ClinVar: Sep 22, 2019 Last updated: Sep 22, 2019 |
Comment:
The variant, NM_005797.3:c.220C>T, was found in the observed patient which is segregated with ARNSHL. The patient showed a characteristic of moderate and progressive hearing loss … (more)
The variant, NM_005797.3:c.220C>T, was found in the observed patient which is segregated with ARNSHL. The patient showed a characteristic of moderate and progressive hearing loss and it was a sporadic case in his family. (less)
Age: 0-9 years
Sex: male
Ethnicity/Population group: Korean
Geographic origin: East Asia
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Likely pathogenic
(Apr 12, 2018)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
biparental
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Molecular Genetics laboratory, Necker Hospital
Accession: SCV004031295.1
First in ClinVar: Sep 03, 2023 Last updated: Sep 03, 2023 |
Clinical Features:
Hearing impairment (present)
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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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MPZL2, Encoding the Epithelial Junctional Protein Myelin Protein Zero-like 2, Is Essential for Hearing in Man and Mouse. | Wesdorp M | American journal of human genetics | 2018 | PMID: 29961571 |
Text-mined citations for rs146689036 ...
HelpRecord last updated Jan 26, 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.