ClinVar Genomic variation as it relates to human health
NM_152783.5(D2HGDH):c.1276G>A (p.Ala426Thr)
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_152783.5(D2HGDH):c.1276G>A (p.Ala426Thr)
Variation ID: 158410 Accession: VCV000158410.56
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q37.3 2: 241755984 (GRCh38) [ NCBI UCSC ] 2: 242695399 (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 5, 2015 Oct 20, 2024 Jan 18, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_152783.5:c.1276G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_689996.4:p.Ala426Thr missense NM_001287249.2:c.874G>A NP_001274178.1:p.Ala292Thr missense NM_001352824.2:c.715G>A NP_001339753.1:p.Ala239Thr missense NR_109778.2:n.1147G>A non-coding transcript variant NC_000002.12:g.241755984G>A NC_000002.11:g.242695399G>A NG_012012.1:g.26370G>A - Protein change
- A426T, A292T, A239T
- Other names
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- Canonical SPDI
- NC_000002.12:241755983: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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0.00200 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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1000 Genomes Project 30x 0.00172
1000 Genomes Project 0.00200
Trans-Omics for Precision Medicine (TOPMed) 0.00387
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00554
The Genome Aggregation Database (gnomAD) 0.00633
The Genome Aggregation Database (gnomAD), exomes 0.00710
Exome Aggregation Consortium (ExAC) 0.00729
- Links
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
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. |
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D2HGDH | - | - |
GRCh38 GRCh37 |
327 | 504 |
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. |
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Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Jul 17, 2017 | RCV000145791.14 | |
Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Dec 1, 2023 | RCV000444247.34 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Jan 18, 2024 | RCV000987080.15 | |
D2HGDH-related disorder
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Benign (1) |
no assertion criteria provided
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Apr 15, 2019 | RCV003917442.2 |
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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Likely benign
(Apr 28, 2015)
|
criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000192928.2
First in ClinVar: Nov 23, 2014 Last updated: Oct 05, 2015 |
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Likely Benign
(Jul 07, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000510958.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
Converted during submission to Likely benign.
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Likely benign
(Jul 17, 2017)
|
criteria provided, single submitter
Method: clinical testing
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Not Specified
Affected status: unknown
Allele origin:
germline
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Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital
Accession: SCV000864338.1
First in ClinVar: Jan 22, 2019 Last updated: Jan 22, 2019 |
Comment:
BS1, BP6; This alteration has an allele frequency that is greater than expected for the associated disease, and was reported as a benign/likely benign alteration … (more)
BS1, BP6; This alteration has an allele frequency that is greater than expected for the associated disease, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory). (less)
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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D-2-hydroxyglutaric aciduria 1
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001136278.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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D-2-hydroxyglutaric aciduria 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000429412.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Benign
(Jan 18, 2024)
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criteria provided, single submitter
Method: clinical testing
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D-2-hydroxyglutaric aciduria 1
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001107582.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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Likely benign
(Dec 01, 2023)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001153393.27
First in ClinVar: Feb 03, 2020 Last updated: Oct 20, 2024 |
Comment:
D2HGDH: BS2
Number of individuals with the variant: 6
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Uncertain significance
(Feb 23, 2016)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000802845.1
First in ClinVar: Aug 04, 2018 Last updated: Aug 04, 2018 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001931583.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001966728.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Benign
(Apr 15, 2019)
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no assertion criteria provided
Method: clinical testing
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D2HGDH-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004737297.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs146578303 ...
HelpRecord last updated Oct 20, 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.