ClinVar Genomic variation as it relates to human health
NM_015021.3(ZNF292):c.6160_6161del (p.Glu2054fs)
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_015021.3(ZNF292):c.6160_6161del (p.Glu2054fs)
Variation ID: 981392 Accession: VCV000981392.20
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 6q14.3 6: 87259788-87259789 (GRCh38) [ NCBI UCSC ] 6: 87969506-87969507 (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 Oct 10, 2020 May 1, 2024 Aug 22, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_015021.3:c.6160_6161del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_055836.1:p.Glu2054fs frameshift NM_001351444.2:c.5740_5741del NP_001338373.1:p.Glu1914fs frameshift NM_015021.1:c.6160_6161delGA NC_000006.12:g.87259789_87259790del NC_000006.11:g.87969507_87969508del NG_054887.1:g.109239_109240del - Protein change
- E1914fs, E2054fs
- Other names
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- Canonical SPDI
- NC_000006.12:87259787:AGA: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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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
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
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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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ZNF292 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
465 | 502 |
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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Likely pathogenic (1) |
criteria provided, single submitter
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Sep 10, 2020 | RCV001260794.4 | |
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Oct 4, 2022 | RCV001292573.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 18, 2020 | RCV001879995.6 | |
Pathogenic (2) |
criteria provided, single submitter
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Feb 18, 2020 | RCV001261752.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 22, 2023 | RCV003353266.2 |
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
(Feb 18, 2020)
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criteria provided, single submitter
Method: clinical testing
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Neurodevelopmental disorder
Affected status: yes
Allele origin:
germline
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Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes
Accession: SCV001572216.1
First in ClinVar: Apr 28, 2021 Last updated: Apr 28, 2021 |
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Likely pathogenic
(Sep 10, 2020)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability
Affected status: yes
Allele origin:
de novo
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Diagnostic Laboratory, Strasbourg University Hospital
Accession: SCV001437887.2
First in ClinVar: Oct 10, 2020 Last updated: Jul 13, 2021 |
Method: targeted next-gen sequencing
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Pathogenic
(Jan 05, 2022)
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criteria provided, single submitter
Method: clinical testing
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Intellectual developmental disorder, autosomal dominant 64
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002061243.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
Comment:
The c.6160_6161del;p.(Glu2054Lysfs*14) is a null frameshift variant (NMD) in the ZNF292 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a … (more)
The c.6160_6161del;p.(Glu2054Lysfs*14) is a null frameshift variant (NMD) in the ZNF292 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevantexon to the transcript -PVS1_strong.The variant was observed to have arisen de novo (paternity confirmed) in a patient with the disease and no family history (PMID: 31723249) -PS2. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 981392; OMIM: 616213.0005; PMID: 31723249) - PS4. This variant is not present in population databases (rs1301328139, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: female
Geographic origin: Brazil
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Pathogenic
(Oct 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Intellectual developmental disorder, autosomal dominant 64
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
maternal
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Genetics Laboratory, UDIAT-Centre Diagnòstic, Hospital Universitari Parc Tauli
Accession: SCV002577721.1
First in ClinVar: Oct 08, 2022 Last updated: Oct 08, 2022 |
Comment:
PVS1_strong;PM2_supporting;PM1;PS4_supporting;PP1
Sex: female
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Likely pathogenic
(Jan 27, 2020)
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criteria provided, single submitter
Method: research
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Intellectual developmental disorder, autosomal dominant 64
Affected status: yes
Allele origin:
de novo
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Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV003840268.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
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Pathogenic
(Jun 29, 2021)
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criteria provided, single submitter
Method: clinical testing
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Intellectual developmental disorder, autosomal dominant 64
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002020945.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Nov 18, 2020)
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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: SCV002215685.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with a neurodevelopmental disorder (PMID: 31723249). In at … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with a neurodevelopmental disorder (PMID: 31723249). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 981392). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu2054Lysfs*14) in the ZNF292 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 670 amino acid(s) of the ZNF292 protein. (less)
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Pathogenic
(Aug 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV004077685.2
First in ClinVar: Oct 28, 2023 Last updated: May 01, 2024 |
Comment:
The c.6160_6161delGA (p.E2054Kfs*14) alteration, located in exon 8 (coding exon 8) of the ZNF292 gene, consists of a deletion of 2 nucleotides from position 6160 … (more)
The c.6160_6161delGA (p.E2054Kfs*14) alteration, located in exon 8 (coding exon 8) of the ZNF292 gene, consists of a deletion of 2 nucleotides from position 6160 to 6161, causing a translational frameshift with a predicted alternate stop codon after 14 amino acids. This alteration occurs at the 3' terminus of the ZNF292 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 24.6% of the protein. However, premature stop codons are typically deleterious in nature, and the impacted region is critical for protein function, and a significant portion of the protein is affected (Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation in multiple individuals with features consistent with ZNF292-related neurodevelopmental disorder (Mirzaa, 2020; Brea-Fernández, 2022). Based on the available evidence, this alteration is classified as pathogenic. (less)
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Likely pathogenic
(-)
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no assertion criteria provided
Method: research
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Neurodevelopmental disorder
Affected status: yes
Allele origin:
de novo
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University of Washington Center for Mendelian Genomics, University of Washington
Accession: SCV001439068.1
First in ClinVar: Oct 25, 2020 Last updated: Oct 25, 2020 |
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Pathogenic
(Feb 18, 2021)
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no assertion criteria provided
Method: literature only
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INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 64
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV001481145.1
First in ClinVar: Feb 28, 2021 Last updated: Feb 28, 2021 |
Comment on evidence:
Mirzaa et al. (2020) reported a recurrent de novo heterozygous 2-bp deletion (6160_6161delGA, NM_015021.2) in exon 8 of the ZNF292 gene, resulting in a frameshift … (more)
Mirzaa et al. (2020) reported a recurrent de novo heterozygous 2-bp deletion (6160_6161delGA, NM_015021.2) in exon 8 of the ZNF292 gene, resulting in a frameshift and premature termination (Glu2054LysfsTer14), in 4 unrelated patients with autosomal dominant intellectual developmental disorder-64 (MRD64; 619188). The mutation was predicted to escape nonsense-mediated decay. It was not present in the gnomAD database (v2.1). The patients included 3 males (patients 17-0013, 17-0014, 19-0001) and 1 female (patient 17-021) of northern European, Iranian, Pakistani, or mixed heritage. Two were aged 18 years and 2 were aged 6 years. All had impaired intellectual development, ranging from mild to severe, and autism. Three were reported as having early hypotonia, which had resolved in one. All had speech delay. One 18-year-old patient was nonverbal and the other 18-year-old was minimally verbal. (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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Trio-based exome sequencing reveals a high rate of the de novo variants in intellectual disability. | Brea-Fernández AJ | European journal of human genetics : EJHG | 2022 | PMID: 35322241 |
De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder. | Mirzaa GM | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 31723249 |
Text-mined citations for rs1301328139 ...
HelpRecord last updated May 01, 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.