ClinVar Genomic variation as it relates to human health
NM_138615.3(DHX30):c.2353C>T (p.Arg785Cys)
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_138615.3(DHX30):c.2353C>T (p.Arg785Cys)
Variation ID: 426111 Accession: VCV000426111.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p21.31 3: 47848246 (GRCh38) [ NCBI UCSC ] 3: 47889736 (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 Jan 6, 2018 May 1, 2024 Feb 12, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_138615.3:c.2353C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_619520.1:p.Arg785Cys missense NM_001330990.2:c.2269C>T NP_001317919.1:p.Arg757Cys missense NM_014966.4:c.2236C>T NP_055781.2:p.Arg746Cys missense NC_000003.12:g.47848246C>T NC_000003.11:g.47889736C>T - Protein change
- R746C, R757C, R785C
- Other names
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- Canonical SPDI
- NC_000003.12:47848245:C:T
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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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DHX30 | - | - |
GRCh38 GRCh37 |
176 | 188 |
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
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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 (2) |
criteria provided, single submitter
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Dec 5, 2017 | RCV000489269.2 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Nov 14, 2023 | RCV000546135.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 12, 2024 | RCV001266616.4 |
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
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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
(Dec 05, 2017)
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criteria provided, single submitter
Method: research
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not provided
Affected status: yes
Allele origin:
de novo
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HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: CSER-HudsonAlpha
Accession: SCV000576476.2 First in ClinVar: May 22, 2017 Last updated: Jan 06, 2018 |
Number of individuals with the variant: 1
Clinical Features:
Intellectual disability, moderate (present) , Delayed speech and language development (present) , Generalized hypotonia (present)
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Pathogenic
(Sep 28, 2018)
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criteria provided, single submitter
Method: clinical testing
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Neurodevelopmental disorder with severe motor impairment and absent language
Affected status: yes
Allele origin:
de novo
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Baylor Genetics
Accession: SCV001528539.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been reported de novo in multiple unrelated individuals with … (more)
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been reported de novo in multiple unrelated individuals with global developmental delay, intellectual disability, severe speech impairment, gait abnormalities, cerebral atrophy, and delayed myelination [PMID 29100085] (less)
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Likely pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Neurodevelopmental disorder with severe motor impairment and absent language
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
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Suma Genomics
Accession: SCV002605333.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Method: Exome sequencing
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Pathogenic
(Nov 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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Neurodevelopmental disorder with severe motor impairment and absent language
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004175984.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
Comment:
Criteria applied: PS2_VSTR,PM2_SUP,PP2,PP3
Clinical Features:
Focal impaired awareness seizure (present) , Intellectual disability (present) , Tonic seizure (present) , Focal-onset seizure (present)
Sex: female
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Pathogenic
(Feb 12, 2024)
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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: SCV001444792.3
First in ClinVar: Nov 21, 2020 Last updated: May 01, 2024 |
Comment:
The c.2353C>T (p.R785C) alteration is located in exon 15 (coding exon 13) of the DHX30 gene. This alteration results from a C to T substitution … (more)
The c.2353C>T (p.R785C) alteration is located in exon 15 (coding exon 13) of the DHX30 gene. This alteration results from a C to T substitution at nucleotide position 2353, causing the arginine (R) at amino acid position 785 to be replaced by a cysteine (C). 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 DHX30-related neurodevelopmental disorder (Lessel, 2017; Ambry internal data). This amino acid position is highly conserved in available vertebrate species. Functional analysis demonstrated that protein with the p.R785C alteration had reduced ATPase activity, abnormal accumulation in the cytoplasm, increased propensity to form stress granules preventing normal translation, and a decreased rate of newly formed peptides (Lessel, 2017). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. (less)
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Pathogenic
(Feb 27, 2023)
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no assertion criteria provided
Method: literature only
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NEURODEVELOPMENTAL DISORDER WITH VARIABLE MOTOR AND SPEECH IMPAIRMENT
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000622125.3
First in ClinVar: Dec 26, 2017 Last updated: Mar 18, 2023 |
Comment on evidence:
In 3 unrelated patients (probands I, J, and K) with neurodevelopmental disorder with severe motor impairment and absent language (NEDMIAL; 617804), Lessel et al. (2017) … (more)
In 3 unrelated patients (probands I, J, and K) with neurodevelopmental disorder with severe motor impairment and absent language (NEDMIAL; 617804), Lessel et al. (2017) identified a de novo heterozygous c.2353C-T transition (c.2353C-T, NM_138615.2) in the DHX30 gene, resulting in an arg785-to-cys (R785C) substitution at a highly conserved residue in motif VI within the helicase core region, which coordinates ATP binding and hydrolysis. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not found in the dbSNP, 1000 Genomes Project, ExAC, or gnomAD databases. (less)
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Pathogenic
(Mar 24, 2020)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
de novo
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Molecular Genetics laboratory, Necker Hospital
Accession: SCV004031353.1
First in ClinVar: Sep 03, 2023 Last updated: Sep 03, 2023 |
Clinical Features:
Intellectual disability (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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De Novo Missense Mutations in DHX30 Impair Global Translation and Cause a Neurodevelopmental Disorder. | Lessel D | American journal of human genetics | 2017 | PMID: 29100085 |
Text-mined citations for rs1085307451 ...
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.