ClinVar Genomic variation as it relates to human health
NM_018486.3(HDAC8):c.490C>T (p.Arg164Ter)
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_018486.3(HDAC8):c.490C>T (p.Arg164Ter)
Variation ID: 39710 Accession: VCV000039710.5
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq13.1 X: 72495216 (GRCh38) [ NCBI UCSC ] X: 71715066 (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 Apr 4, 2013 Dec 24, 2022 May 8, 2019 - HGVS
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Nucleotide Protein Molecular
consequenceNM_018486.3:c.490C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060956.1:p.Arg164Ter nonsense NM_001166418.2:c.217C>T NP_001159890.1:p.Arg73Ter nonsense NM_001166419.2:c.490C>T NP_001159891.1:p.Arg164Ter nonsense NM_001166448.2:c.217C>T NP_001159920.1:p.Arg73Ter nonsense NR_051952.2:n.430C>T non-coding transcript variant NC_000023.11:g.72495216G>A NC_000023.10:g.71715066G>A NG_015851.1:g.82888C>T - Protein change
- R164*, R73*
- Other names
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- Canonical SPDI
- NC_000023.11:72495215: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
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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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HDAC8 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
304 | 436 |
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
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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 (4) |
criteria provided, multiple submitters, no conflicts
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May 8, 2019 | RCV000032915.14 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 9, 2017 | RCV000480167.1 |
Submissions - Germline
Classification
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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
(Sep 19, 2014)
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criteria provided, single submitter
Method: clinical testing
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Cornelia de Lange syndrome 5
(X-linked inheritance)
Affected status: yes
Allele origin:
de novo
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Baylor Genetics
Study: Adult_WES
Accession: SCV000245489.1 First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015 |
Comment:
This variant has been previously reported as disease-causing and was found once in our laboratory de novo in a 21-year-old female with autism, intellectual disability, … (more)
This variant has been previously reported as disease-causing and was found once in our laboratory de novo in a 21-year-old female with autism, intellectual disability, hypotonia, hyperextensibility, cardiomyopathy, scoliosis, dysautonomia (less)
Number of individuals with the variant: 1
Age: 20-29 years
Sex: female
Ethnicity/Population group: Causasians
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Pathogenic
(Mar 09, 2017)
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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: SCV000565055.3
First in ClinVar: Apr 27, 2017 Last updated: Apr 27, 2017 |
Comment:
The R164X variant in the HDAC8 gene has been reported previously as heterozygous de novo in a female with Cornelia de Lange syndrome who exhibited … (more)
The R164X variant in the HDAC8 gene has been reported previously as heterozygous de novo in a female with Cornelia de Lange syndrome who exhibited growth delays, absent speech, dysmorphic facial features, asymmetric skull, limb length discrepancy and dysplastic kidneys (Deardorff et al., 2012). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R164X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret R164X as a pathogenic variant. (less)
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Pathogenic
(Nov 10, 2016)
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criteria provided, single submitter
Method: research
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Cornelia de Lange syndrome 5
Affected status: yes
Allele origin:
unknown
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HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: CSER-HudsonAlpha
Accession: SCV000484415.3 First in ClinVar: Sep 29, 2015 Last updated: Dec 24, 2022 |
Number of individuals with the variant: 1
Clinical Features:
Global developmental delay (present) , Microcephaly (present) , Gastroesophageal reflux (present) , Ventriculomegaly (present) , Anal atresia (present) , Atrioventricular canal defect (present) , Supernumerary … (more)
Global developmental delay (present) , Microcephaly (present) , Gastroesophageal reflux (present) , Ventriculomegaly (present) , Anal atresia (present) , Atrioventricular canal defect (present) , Supernumerary nipple (present) , Arachnoid cyst (present) , Delayed speech and language development (present) (less)
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Pathogenic
(May 08, 2019)
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criteria provided, single submitter
Method: clinical testing
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CORNELIA DE LANGE SYNDROME 5
Affected status: yes
Allele origin:
germline
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Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV001445900.1
First in ClinVar: Nov 21, 2020 Last updated: Nov 21, 2020 |
Comment:
This nonsense variant found in exon 5 of 11 is predicted to result in loss of normal protein function. This variant has been previously reported … (more)
This nonsense variant found in exon 5 of 11 is predicted to result in loss of normal protein function. This variant has been previously reported as a de novo change in patients with Cornelia de Lange syndrome (PMID: 22885700). It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. Analysis 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.490C>T (p.Arg164Ter) variant is classified as Pathogenic. (less)
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Pathogenic
(Sep 13, 2012)
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no assertion criteria provided
Method: literature only
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CORNELIA DE LANGE SYNDROME 5
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000056687.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In a 6-year-old female with features consistent with Cornelia de Lange syndrome (CDLS5; 300882), Deardorff et al. (2012) identified a heterozygous de novo C-to-T transition … (more)
In a 6-year-old female with features consistent with Cornelia de Lange syndrome (CDLS5; 300882), Deardorff et al. (2012) identified a heterozygous de novo C-to-T transition at nucleotide 490 of the HDAC8 gene resulting in an arg-to-ter codon substitution at codon 164 (R164X). The patient had growth delays, absent speech, and characteristic facial features as well as asymmetric skull, limb length discrepancy, and dysplastic kidneys. This mutation was not seen in 290 ethnically matched control chromosomes or in 629 individuals of the 1000 Genomes Project. (less)
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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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Molecular diagnostic experience of whole-exome sequencing in adult patients. | Posey JE | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26633545 |
HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. | Deardorff MA | Nature | 2012 | PMID: 22885700 |
Text-mined citations for rs397515415 ...
HelpRecord last updated Dec 24, 2022
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.