ClinVar Genomic variation as it relates to human health
NM_205861.3(DHDDS):c.110G>A (p.Arg37His)
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(5); Likely pathogenic(1); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_205861.3(DHDDS):c.110G>A (p.Arg37His)
Variation ID: 451635 Accession: VCV000451635.17
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 1p36.11 1: 26438214 (GRCh38) [ NCBI UCSC ] 1: 26764705 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 19, 2017 Feb 14, 2024 Nov 29, 2022 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_205861.3:c.110G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_995583.1:p.Arg37His missense NM_001243564.2:c.110G>A NP_001230493.1:p.Arg37His missense NM_001243565.2:c.110G>A NP_001230494.1:p.Arg37His missense NM_001319959.2:c.-193G>A 5 prime UTR NM_024887.4:c.110G>A NP_079163.2:p.Arg37His missense NC_000001.11:g.26438214G>A NC_000001.10:g.26764705G>A NG_029786.1:g.10933G>A - Protein change
- R37H
- Other names
- -
- Canonical SPDI
- NC_000001.11:26438213:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
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 | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
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. |
|||
DHDDS | - | - |
GRCh38 GRCh37 |
545 | 554 |
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
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2021 | RCV000519248.3 | |
Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
|
Nov 29, 2022 | RCV000578122.10 | |
Pathogenic (1) |
criteria provided, single submitter
|
Sep 7, 2022 | RCV001858011.5 |
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. |
|
---|---|---|---|---|---|
Likely pathogenic
(Feb 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001480068.1
First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
Clinical Features:
Saccadic smooth pursuit (present) , Intellectual disability (present) , Seizure (present) , Cerebellar ataxia (present) , Hypertonia (present) , Gait disturbance (present) , Dysdiadochokinesis (present) … (more)
Saccadic smooth pursuit (present) , Intellectual disability (present) , Seizure (present) , Cerebellar ataxia (present) , Hypertonia (present) , Gait disturbance (present) , Dysdiadochokinesis (present) , Intention tremor (present) , Postural tremor (present) (less)
Sex: female
|
|
Pathogenic
(Jun 24, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000620358.3
First in ClinVar: Dec 19, 2017 Last updated: Jun 23, 2021 |
Comment:
Not observed in large population cohorts (Lek et al., 2016) In silico analysis supports that this missense variant has a deleterious effect on protein structure/function … (more)
Not observed in large population cohorts (Lek et al., 2016) In silico analysis supports that this missense variant has a deleterious effect on protein structure/function This variant is associated with the following publications: (PMID: 29100083, 31780880) (less)
|
|
Uncertain significance
(Mar 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Developmental delay and seizures with or without movement abnormalities
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001934465.1
First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
Comment:
Despite strong evidence for its pathogenicity, this variant has to be classified as of unknown significance, according to the ACMG-criteria (Richards et al., 2015)
|
|
Pathogenic
(Dec 22, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Developmental delay and seizures with or without movement abnormalities
Affected status: yes
Allele origin:
germline
|
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV002061811.2
First in ClinVar: Jan 22, 2022 Last updated: Feb 11, 2022 |
Comment:
PS2, PS4, PP3, PM2
|
|
Pathogenic
(Sep 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Developmental delay and seizures with or without movement abnormalities
Affected status: yes
Allele origin:
germline
|
3billion
Accession: SCV002572747.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
This missense variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene … (more)
This missense variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.76; 3Cnet: 0.49). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000451635). The variant has been previously reported as de novo in a similarly affected individual (PMID: 29100083 , 29100083). A different missense change at the same codon (p.Arg37Cys) has been reported to be associated with DHDDS-related disorder (ClinVar ID: VCV001214981). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Autism (present) , Myoclonus (present)
|
|
Pathogenic
(Nov 29, 2022)
|
criteria provided, single submitter
Method: research
|
Developmental delay and seizures with or without movement abnormalities
Affected status: yes
Allele origin:
germline
|
Laboratory of Medical Genetics, University of Torino
Study: NeuroWES
Accession: SCV002760060.1 First in ClinVar: Dec 11, 2022 Last updated: Dec 11, 2022 |
|
|
Pathogenic
(Sep 07, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Retinitis pigmentosa 59
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002216078.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict … (more)
This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 451635). This missense change has been observed in individual(s) with autosomal dominant developmental and epileptic encephalopathy (PMID: 29100083, 31780880). In at least one individual the variant was observed to be de novo. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 37 of the DHDDS protein (p.Arg37His). (less)
|
|
Pathogenic
(Jan 24, 2018)
|
no assertion criteria provided
Method: literature only
|
DEVELOPMENTAL DELAY AND SEIZURES WITH OR WITHOUT MOVEMENT ABNORMALITIES
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000679984.1
First in ClinVar: Jan 29, 2018 Last updated: Jan 29, 2018 |
Comment on evidence:
In 2 unrelated patients (indvSG and HSJ0762) with developmental delay and seizures with or without movement abnormalities (DEDSM; 617836), Hamdan et al. (2017) identified a … (more)
In 2 unrelated patients (indvSG and HSJ0762) with developmental delay and seizures with or without movement abnormalities (DEDSM; 617836), Hamdan et al. (2017) identified a de novo heterozygous c.110G-A transition (c.110G-A, NM_024887.3) in the DHDDS gene, resulting in an arg37-to-his (R37H) substitution at a conserved residue in the catalytic domain. The mutation, which was found by whole-exome or whole-genome sequencing and confirmed by Sanger sequencing, was filtered against public databases, including the Exome Variant Server, 1000 Genomes Project, and ExAC. Functional studies of the variant and studies of patient cells were not performed, but the authors postulated a gain-of-function or dominant-negative effect. (less)
|
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 |
---|---|---|---|---|
Rare Variants in 48 Genes Account for 42% of Cases of Epilepsy With or Without Neurodevelopmental Delay in 246 Pediatric Patients. | Fernández-Marmiesse A | Frontiers in neuroscience | 2019 | PMID: 31780880 |
High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies. | Hamdan FF | American journal of human genetics | 2017 | PMID: 29100083 |
Text-mined citations for rs1553121073 ...
HelpRecord last updated Feb 14, 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.