ClinVar Genomic variation as it relates to human health
NM_000033.4(ABCD1):c.1825G>A (p.Glu609Lys)
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_000033.4(ABCD1):c.1825G>A (p.Glu609Lys)
Variation ID: 166626 Accession: VCV000166626.27
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 153743031 (GRCh38) [ NCBI UCSC ] X: 153008485 (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, 2018 Jun 17, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000033.4:c.1825G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000024.2:p.Glu609Lys missense NC_000023.11:g.153743031G>A NC_000023.10:g.153008485G>A NG_009022.2:g.23164G>A LRG_1017:g.23164G>A LRG_1017t1:c.1825G>A LRG_1017p1:p.Glu609Lys P33897:p.Glu609Lys - Protein change
- E609K
- Other names
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- Canonical SPDI
- NC_000023.11:153743030: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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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00009
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
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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ABCD1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1510 | 1755 |
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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Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000152721.28 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Apr 14, 2023 | RCV000723952.21 |
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
(Apr 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics
Accession: SCV001880338.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with clinical … (more)
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with clinical features associated with this gene. Computational tools predict that this variant is damaging. (less)
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Pathogenic
(Jul 19, 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: SCV001815258.3
First in ClinVar: Sep 08, 2021 Last updated: Mar 04, 2023 |
Comment:
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: 27766264, … (more)
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: 27766264, 21966424, 20661612, 23891399, 21476988, 11748843, 15800013, 21068741, 24480483, 8892025, 19892975, 7825602, 15811009, 8566952, 30902905, 32954314) (less)
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Pathogenic
(Aug 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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Adrenoleukodystrophy
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV003835019.2
First in ClinVar: Mar 11, 2023 Last updated: Oct 06, 2023 |
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Pathogenic
(Apr 14, 2023)
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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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Revvity Omics, Revvity
Accession: SCV004238276.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
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Pathogenic
(May 01, 2014)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000202107.7
First in ClinVar: Jan 30, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Sep 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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Adrenoleukodystrophy
Affected status: unknown
Allele origin:
germline
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Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV001431534.1
First in ClinVar: Sep 05, 2020 Last updated: Sep 05, 2020 |
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Pathogenic
(Nov 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Adrenoleukodystrophy
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002045842.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
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Pathogenic
(Dec 25, 2023)
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criteria provided, single submitter
Method: clinical testing
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Adrenoleukodystrophy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000629996.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 609 of the ABCD1 protein … (more)
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 609 of the ABCD1 protein (p.Glu609Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with adrenoleukodystrophy (ALD), adrenomyeloneuropathy (AMN), and adult cerebral adrenoleukodystrophy (PMID: 7825602, 11748843, 20661612, 21966424). ClinVar contains an entry for this variant (Variation ID: 166626). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCD1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ABCD1 function (PMID: 21476988). This variant disrupts the p.Glu609 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7825602, 21476988). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(May 12, 2023)
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criteria provided, single submitter
Method: clinical testing
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Adrenoleukodystrophy
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004231790.2
First in ClinVar: Jan 26, 2024 Last updated: May 12, 2024 |
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Pathogenic
(Feb 01, 2024)
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criteria provided, single submitter
Method: curation
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Adrenoleukodystrophy
Affected status: no
Allele origin:
germline
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Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV005051832.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 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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Clinical efficacy of haematopoietic stem cell transplantation for adult adrenoleukodystrophy. | Matsukawa T | Brain communications | 2020 | PMID: 32954314 |
Detection of unusual very-long-chain fatty acid and ether lipid derivatives in the fibroblasts and plasma of patients with peroxisomal diseases using liquid chromatography-mass spectrometry. | Takashima S | Molecular genetics and metabolism | 2017 | PMID: 28089346 |
Generation of human embryonic stem cells from abnormal blastocyst diagnosed with adrenoleukodystrophy. | Ouyang Q | Stem cell research | 2016 | PMID: 27934597 |
ABC Transporter Subfamily D: Distinct Differences in Behavior between ABCD1-3 and ABCD4 in Subcellular Localization, Function, and Human Disease. | Kawaguchi K | BioMed research international | 2016 | PMID: 27766264 |
X-linked adrenoleukodystrophy in women: a cross-sectional cohort study. | Engelen M | Brain : a journal of neurology | 2014 | PMID: 24480483 |
Genomic profiling identifies novel mutations and SNPs in ABCD1 gene: a molecular, biochemical and clinical analysis of X-ALD cases in India. | Kumar N | PloS one | 2011 | PMID: 21966424 |
Conservation of targeting but divergence in function and quality control of peroxisomal ABC transporters: an analysis using cross-kingdom expression. | Zhang X | The Biochemical journal | 2011 | PMID: 21476988 |
X-linked adrenoleukodystrophy: diagnostic and follow-up system in Japan. | Shimozawa N | Journal of human genetics | 2011 | PMID: 21068741 |
Identification of novel SNPs of ABCD1, ABCD2, ABCD3, and ABCD4 genes in patients with X-linked adrenoleukodystrophy (ALD) based on comprehensive resequencing and association studies with ALD phenotypes. | Matsukawa T | Neurogenetics | 2011 | PMID: 20661612 |
Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. | Cartier N | Science (New York, N.Y.) | 2009 | PMID: 19892975 |
X-linked adrenoleukodystrophy in Spain. Identification of 26 novel mutations in the ABCD1 gene in 80 patients. Improvement of genetic counseling in 162 relative females. | Coll MJ | Clinical genetics | 2005 | PMID: 15811009 |
Decreased expression of ABCD4 and BG1 genes early in the pathogenesis of X-linked adrenoleukodystrophy. | Asheuer M | Human molecular genetics | 2005 | PMID: 15800013 |
ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations. | Kemp S | Human mutation | 2001 | PMID: 11748843 |
Identification of mutations in the ALD-gene of 20 families with adrenoleukodystrophy/adrenomyeloneuropathy. | Krasemann EW | Human genetics | 1996 | PMID: 8566952 |
Spectrum of mutations in the gene encoding the adrenoleukodystrophy protein. | Ligtenberg MJ | American journal of human genetics | 1995 | PMID: 7825602 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ABCD1 | - | - | - | - |
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Text-mined citations for rs150346282 ...
HelpRecord last updated Sep 08, 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.