ClinVar Genomic variation as it relates to human health
NM_004247.4(EFTUD2):c.2562-2_2562-1del
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(1); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004247.4(EFTUD2):c.2562-2_2562-1del
Variation ID: 984919 Accession: VCV000984919.6
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 17q21.31 17: 44852563-44852564 (GRCh38) [ NCBI UCSC ] 17: 42929931-42929932 (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 Nov 21, 2020 Apr 6, 2024 Mar 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004247.4:c.2562-2_2562-1del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_001142605.2:c.2457-2_2457-1del splice acceptor NM_001258353.1:c.2562-2_2562-1del NM_001258353.2:c.2562-2_2562-1del splice acceptor NM_001258354.2:c.2532-2_2532-1del splice acceptor NC_000017.11:g.44852563_44852564del NC_000017.10:g.42929931_42929932del NG_032674.1:g.52062_52063del - Protein change
- Other names
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- Canonical SPDI
- NC_000017.11:44852562:CT:
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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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- Links
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
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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EFTUD2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
644 | 654 |
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
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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 (3) |
criteria provided, conflicting classifications
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Mar 25, 2024 | RCV001265543.4 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 14, 2022 | RCV003235522.2 |
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
(Dec 20, 2019)
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criteria provided, single submitter
Method: clinical testing
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MANDIBULOFACIAL DYSOSTOSIS, GUION-ALMEIDA TYPE
Affected status: yes
Allele origin:
germline
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Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV001443693.1
First in ClinVar: Nov 21, 2020 Last updated: Nov 21, 2020 |
Comment:
This variant affects the canonical splice acceptor site of intron 25 and is therefore predicted to interfere with splicing and result in loss of normal … (more)
This variant affects the canonical splice acceptor site of intron 25 and is therefore predicted to interfere with splicing and result in loss of normal protein function. This variant has been previously reported as a heterozygous change in an affected male and his mildly affected mother, and a heterozygous change in an unrelated patient with Mandibulofacial Dysostosis, Guion-Almeida Type, including mandibulofacial dysostosis, dysplastic ear, and retrognathia (PMID: 24470203). It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. Multiple splice prediction tools suggest this variant is likely to interfere with normal splicingAnalysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.2562-2_2562-1del variant is classified as Pathogenic. (less)
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Likely pathogenic
(Jan 25, 2022)
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criteria provided, single submitter
Method: clinical testing
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Mandibulofacial dysostosis-microcephaly syndrome
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002580601.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Dec 14, 2022)
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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: SCV003933609.1
First in ClinVar: Jun 24, 2023 Last updated: Jun 24, 2023 |
Comment:
Reported in individuals with mandibulofacial dysostosis with microcephaly in published literature (Lehalle et al., 2014); Canonical splice site variant predicted to result in a null … (more)
Reported in individuals with mandibulofacial dysostosis with microcephaly in published literature (Lehalle et al., 2014); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24470203) (less)
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Pathogenic
(Nov 23, 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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Invitae
Accession: SCV004298236.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, … (more)
Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 984919). Disruption of this splice site has been observed in individuals with mandibulofacial dysostosis (PMID: 24470203). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a splice site in intron 25 of the EFTUD2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in EFTUD2 are known to be pathogenic (PMID: 24999515, 26507355). (less)
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Uncertain significance
(Mar 25, 2024)
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criteria provided, single submitter
Method: research
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Mandibulofacial dysostosis-microcephaly syndrome
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004805309.2
First in ClinVar: Mar 30, 2024 Last updated: Apr 06, 2024 |
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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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Mandibulofacial Dysostosis with Microcephaly. | Adam MP | - | 2023 | PMID: 24999515 |
Mandibulofacial Dysostosis with Microcephaly: Mutation and Database Update. | Huang L | Human mutation | 2016 | PMID: 26507355 |
Delineation of EFTUD2 haploinsufficiency-related phenotypes through a series of 36 patients. | Lehalle D | Human mutation | 2014 | PMID: 24470203 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Text-mined citations for rs2050474390 ...
HelpRecord last updated Apr 06, 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.