ClinVar Genomic variation as it relates to human health
NM_001360.3(DHCR7):c.964-1G>C
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_001360.3(DHCR7):c.964-1G>C
Variation ID: 93725 Accession: VCV000093725.109
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.4 11: 71435840 (GRCh38) [ NCBI UCSC ] 11: 71146886 (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 May 19, 2024 May 6, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001360.3:c.964-1G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_001163817.2:c.964-1G>C splice acceptor NC_000011.10:g.71435840C>G NC_000011.9:g.71146886C>G NG_012655.2:g.17592G>C LRG_340:g.17592G>C LRG_340t1:c.964-1G>C - Protein change
- Other names
- IVS8-1G>C
- Canonical SPDI
- NC_000011.10:71435839:C:G
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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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0.00260 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00250
1000 Genomes Project 0.00260
Trans-Omics for Precision Medicine (TOPMed) 0.00466
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00544
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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DHCR7 | - | - |
GRCh38 GRCh37 |
917 | 932 |
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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Pathogenic (13) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2024 | RCV000079661.50 | |
Pathogenic/Likely pathogenic (34) |
criteria provided, multiple submitters, no conflicts
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May 6, 2024 | RCV000180570.70 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 20, 2021 | RCV000623789.12 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 6, 2020 | RCV001263353.9 | |
See cases
|
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 17, 2023 | RCV002251968.10 |
DHCR7-related disorder
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Pathogenic (1) |
criteria provided, single submitter
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Feb 8, 2024 | RCV003390775.5 |
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. |
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Pathogenic
(Jan 21, 2016)
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criteria provided, single submitter
Method: clinical testing
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Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697859.1
First in ClinVar: Jan 06, 2018 Last updated: Jan 06, 2018 |
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Pathogenic
(Jul 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Smith-Lemli-Opitz syndrome
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743877.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Pathogenic
(Jan 25, 2016)
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criteria provided, single submitter
Method: clinical testing
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Smith-Lemli-Opitz syndrome
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000745303.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Likely pathogenic
(Oct 11, 2017)
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criteria provided, single submitter
Method: clinical testing
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Smith-Lemli-Opitz syndrome
Affected status: yes
Allele origin:
unknown
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Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Study: Clinvar_gadteam_Clinical_exome_analysis_3
Accession: SCV000803783.1 First in ClinVar: Aug 24, 2018 Last updated: Aug 24, 2018 |
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Pathogenic
(Oct 18, 2019)
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criteria provided, single submitter
Method: clinical testing
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Smith-Lemli-Opitz syndrome
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001251430.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
The variant was confirmed as compound heterozygous with a pathogenic variant (NM_001163817.1: c.452G>A).
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Pathogenic
(Oct 10, 2019)
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criteria provided, single submitter
Method: clinical testing
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Smith-Lemli-Opitz syndrome
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000247185.2
First in ClinVar: Oct 05, 2015 Last updated: Jun 15, 2020 |
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Pathogenic
(Nov 12, 2019)
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criteria provided, single submitter
Method: clinical testing
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Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV001193925.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 06, 2020 |
Comment:
NM_001360.2(DHCR7):c.964-1G>C is classified as pathogenic in the context of Smith-Lemli-Opitz syndrome and is associated with the severe form of the disease. Sources cited for classification … (more)
NM_001360.2(DHCR7):c.964-1G>C is classified as pathogenic in the context of Smith-Lemli-Opitz syndrome and is associated with the severe form of the disease. Sources cited for classification include the following: PMID 15952211 and 10677299. Classification of NM_001360.2(DHCR7):c.964-1G>C is based on the following criteria: The variant is located at a canonical splice site, is expected to disrupt gene function and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening. (less)
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Pathogenic
(Feb 06, 2020)
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criteria provided, single submitter
Method: clinical testing
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Global developmental delay
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
New York Genome Center
Study: CSER-NYCKidSeq
Accession: SCV001441395.1 First in ClinVar: Nov 06, 2020 Last updated: Nov 06, 2020 |
Secondary finding: no
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447515.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Global developmental delay (present) , Syndactyly (present)
Sex: female
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Pathogenic
(Sep 26, 2018)
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criteria provided, single submitter
Method: clinical testing
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Smith-Lemli-Opitz syndrome
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001367096.2
First in ClinVar: Jul 06, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PM2.
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Pathogenic
(Jul 22, 2021)
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criteria provided, single submitter
Method: clinical testing
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Smith-Lemli-Opitz syndrome
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001810398.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Sex: mixed
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Pathogenic
(Sep 22, 2020)
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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: SCV000613096.3
First in ClinVar: Dec 19, 2017 Last updated: Sep 19, 2021 |
Comment:
This variant is expected to severely impact normal RNA splicing, and consequently, protein structure and/or function. The frequency of this variant in the general population … (more)
This variant is expected to severely impact normal RNA splicing, and consequently, protein structure and/or function. The frequency of this variant in the general population is higher than would generally be expected for pathogenic variants in this gene (http://gnomad.broadinstitute.org); however DHC7 c.964-1G>C is reported to account for 1/3rd of all pathogenic alleles and described as a founder variant (PMID:11175299,17965227,16906538). Assessment of experimental evidence suggests this variant results in abnormal protein function. RT-PCR study showed that disruption of this splice site led to a premature stop codon (PMID:9653161). In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. (less)
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Pathogenic
(Sep 17, 2021)
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criteria provided, single submitter
Method: clinical testing
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Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001157268.3
First in ClinVar: Feb 10, 2020 Last updated: Jan 08, 2022 |
Comment:
The DHCR7 c.964-1G>C variant (rs138659167) is reported in the literature as the most common variant in individuals affected with Smith-Lemli-Opitz (SLO) syndrome (reviewed in Witsch-Baumgartner … (more)
The DHCR7 c.964-1G>C variant (rs138659167) is reported in the literature as the most common variant in individuals affected with Smith-Lemli-Opitz (SLO) syndrome (reviewed in Witsch-Baumgartner 2015), found in both the homozygous and compound heterozygous state (Fitzky 1998, Krakowiak 2000, Witsch-Baumgartner 2000). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 93725), and is found in the general population with an overall allele frequency of 0.39% (1,010/262,084 alleles) in the Genome Aggregation Database. This variant disrupts the canonical splice acceptor site of intron 8, which is likely to disrupt gene function. Functional studies from patient mRNA show an insertion of 134 nucleotides between exons 8 and 9, leading to a premature termination codon (Fitzky 1998). Based on available information, the c.964-1G>C variant is considered to be pathogenic. References: Fitzky BU et al. Mutations in the Delta7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome. Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8181-6. Krakowiak PA et al. Mutation analysis and description of sixteen RSH/Smith-Lemli-Opitz syndrome patients: polymerase chain reaction-based assays to simplify genotyping. Am J Med Genet. 2000 94(3):214-27. Witsch-Baumgartner M et al. Mutational spectrum in the Delta7-sterol reductase gene and genotype-phenotype correlation in 84 patients with Smith-Lemli-Opitz syndrome. Am J Hum Genet. 2000 66(2):402-12. Witsch-Baumgartner M and Lanthaler B. et al. Birthday of a syndrome: 50 years anniversary of Smith-Lemli-Opitz Syndrome. Eur J Hum Genet. 2015 Mar;23(3):277-8. (less)
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Pathogenic
(Oct 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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Smith-Lemli-Opitz syndrome
Affected status: yes
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV002061655.3
First in ClinVar: Jan 22, 2022 Last updated: Aug 05, 2023 |
Comment:
PVS1, PM3_strong
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Pathogenic
(Nov 08, 2021)
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criteria provided, single submitter
Method: clinical testing
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Smith-Lemli-Opitz syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002761501.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
Comment:
The DHCR7 c.964-1G>C variant is located at the splice acceptor site in intron 8 and has been shown to cause aberrant mRNA splicing and insertion … (more)
The DHCR7 c.964-1G>C variant is located at the splice acceptor site in intron 8 and has been shown to cause aberrant mRNA splicing and insertion of 134bp of intron DNA sequence resulting in a frameshift that prematurely truncates the protein (PMID: 9653161) (PVS1). The variant is the most common pathogenic variant in the DHCR7 gene (approx 29% of SLOS alleles), and has been reported in multiple patients with autosomal recessive Smith-Lemli-Opitz syndrome (SLOS) in both the homozygous or compound heterozygous state (PMID: 24824134, 23042628, 10814720, 10995508, 11427181 and ClinVar ID:93725) (PS4). The variant is in gnomAD (647/152,210 heterozygotes, 0 homozygotes ). The variant has been reported as Pathogenic/Likely pathogenic by other diagnostic laboratories (ClinVar Variation ID: 93725) and has been reported in the HGMD database: CS982160. (less)
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Pathogenic
(Mar 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001163695.3
First in ClinVar: Mar 01, 2020 Last updated: Oct 06, 2023 |
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Pathogenic
(Nov 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
maternal
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Daryl Scott Lab, Baylor College of Medicine
Accession: SCV004102682.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
|
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Pathogenic
(Oct 12, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002020377.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
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Pathogenic
(Feb 08, 2024)
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criteria provided, single submitter
Method: clinical testing
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DHCR7-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004110145.2
First in ClinVar: Nov 20, 2023 Last updated: Mar 16, 2024 |
Comment:
The DHCR7 c.964-1G>C variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This canonical splice variant, often referred to … (more)
The DHCR7 c.964-1G>C variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This canonical splice variant, often referred to in earlier literature as IVS8-1G>C, has been documented as causative for Smith-Lemli-Opitz syndrome (SLOS) (Fitzky et al. 1998. PubMed ID: 9653161; Witsch-Baumgartner et al. 2000. PubMed ID: 10677299). RT-PCR studies have shown that the c.964-1G>C variant results in the use of an alternative splice acceptor site, resulting in the insertion of 134 bp of intronic DNA sequence and subsequent premature termination (Fitzky et al. 1998. PubMed ID: 9653161). This variant has been reported in the ClinVar database as pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/93725/) and is reported in 1.2% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Oct 17, 2023)
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criteria provided, single submitter
Method: clinical testing
|
see cases
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University Hospital Muenster
Accession: SCV004801706.1
First in ClinVar: Mar 23, 2024 Last updated: Mar 23, 2024 |
Comment:
ACMG categories: PVS1,PM1,PM2,BS1
Number of individuals with the variant: 1
Clinical Features:
Abnormal cardiovascular system morphology (present) , Infantile muscular hypotonia (present) , Syndactyly (present) , Cleft palate (present) , Clubfoot (present) , Wide nose (present) , … (more)
Abnormal cardiovascular system morphology (present) , Infantile muscular hypotonia (present) , Syndactyly (present) , Cleft palate (present) , Clubfoot (present) , Wide nose (present) , Nevus flammeus nuchae (present) , Microretrognathia (present) (less)
Age: 0-9 years
Sex: female
Tissue: blood
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Pathogenic
(Oct 11, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000711716.2
First in ClinVar: Apr 09, 2018 Last updated: Apr 20, 2024 |
Comment:
The c.964-1G>C variant in DHCR7 has been reported in >50 patients with Smith-Lemli-Opitz syndrome (SLO) who were either homozygous or compound heterozygous for this variant … (more)
The c.964-1G>C variant in DHCR7 has been reported in >50 patients with Smith-Lemli-Opitz syndrome (SLO) who were either homozygous or compound heterozygous for this variant (Fitzky 1998 PMID: 9653161, Krakowiak 2000 PMID: 10995508, Witsch-Baumgartner 2000 PMID: 10677299). It is one of the most common variants reported in patients with this disorder. This variant has also been reported in ClinVar (Variation ID 93725) and identified in 1.3% (44/3472) of Ashkenazi Jewish chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2), which is consistent with the carrier frequency for SLO. This variant occurs in the invariant region (+/- 1,2) of the splice consensus sequence in the last intron/exon junction and is predicted to cause altered splicing leading to an abnormal protein. Functional studies using RT-PCR of patient mRNA isolated from fibroblasts show that that this variant leads to the use of an alternative splice acceptor in intron 8, which results in the insertion of 134 bp of intronic sequence, and ultimately a frameshift and premature termination with >10% of the protein affected (Fitzky 1998 PMID: 9653161). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive SLO syndrome. ACMG/AMP Criteria applied: PVS1_Strong, PM3_VeryStrong. (less)
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Pathogenic
(Aug 20, 2021)
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criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000848264.5
First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024 |
Comment:
The c.964-1G>C intronic variant results from a G to C substitution one nucleotide before exon 9 (coding exon 7) of the DHCR7 gene. Alterations that … (more)
The c.964-1G>C intronic variant results from a G to C substitution one nucleotide before exon 9 (coding exon 7) of the DHCR7 gene. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. Based on data from gnomAD, the C allele has an overall frequency of 0.385% (1010/262084) total alleles studied. The highest observed frequency was 1.182% (116/9812) of Ashkenazi Jewish alleles. This alteration is one of the most common DHCR7 mutations in North America and Western Europe, and was found to account for 35% of mutations in a cohort of 263 individuals with Smith-Lemli-Optiz syndrome (SLOS) (Witsch-Baumgartner, 2008). This mutation was reported in the homozygous state in a fetus with holoprosencephaly and multiple congenital anomalies as well as in newborns with a severe phenotype (Nowaczyk, 2001). This nucleotide position is highly conserved in available vertebrate species. Analysis of cDNA isolated from fibroblasts of a compound heterozygous individual with this alteration demonstrated the use of an alternative splice acceptor site, leading to a transcript with a shift in reading frame and a premature stop codon (Fitzky, 1998). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Based on the available evidence, this alteration is classified as pathogenic. (less)
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Pathogenic
(Apr 20, 2022)
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criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
inherited
|
New York Genome Center
Study: PrenatalSEQ
Accession: SCV004046609.2 First in ClinVar: Oct 21, 2023 Last updated: May 19, 2024 |
Comment:
The inherited c.964-1G>C splice site variant identified in the DHCR7 gene is a known pathogenic variant and is the most common variant detected in individuals … (more)
The inherited c.964-1G>C splice site variant identified in the DHCR7 gene is a known pathogenic variant and is the most common variant detected in individuals affected with SLOS (found in approximately 30% of patients). It has been reported in the literature in both the homozygous and compound heterozygous state [PMID: 23042628, 24824134]. This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 93725). The varian thas .004251 allele frequency in the gnomAD(v3) database (647 out of 152210 heterozygous alleles, no homozygotes). The variant affects the canonical splice acceptor site in intron 8 (the last intron, transcript NM_001360.2) of DHRC7 gene. In vitro functional studies showed that the variant causes aberrant mRNA splicing resulting in insertion of 134 nucleotides which alters the wild type translational reading frame and introduces a premature translation termination codon [PMID: 9653161]. Based on the available evidence, the inherited c.964-1G>C splice site variant is reported as Pathogenic. (less)
Clinical Features:
Renal agenesis (present) , Renal cyst (present) , Cystic renal dysplasia (present) , Abnormality of the bladder (present) , Oligohydramnios (present) , Left ventricular hypertrophy … (more)
Renal agenesis (present) , Renal cyst (present) , Cystic renal dysplasia (present) , Abnormality of the bladder (present) , Oligohydramnios (present) , Left ventricular hypertrophy (present) , Right ventricular hypertrophy (present) (less)
Age: 30-39 weeks gestation
Secondary finding: no
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Pathogenic
(Jul 18, 2016)
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criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: no
Allele origin:
germline
|
Knight Diagnostic Laboratories, Oregon Health and Sciences University
Study: CSER-NextGen
Accession: SCV000494249.1 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Comment:
The c.964-1G>C splice variant in the DHCR7 gene has been previously reported in multiple individuals affected with Smith-Lemli-Opitz Syndrome (Witsch-Baumgartner et al., 2000; Jira et … (more)
The c.964-1G>C splice variant in the DHCR7 gene has been previously reported in multiple individuals affected with Smith-Lemli-Opitz Syndrome (Witsch-Baumgartner et al., 2000; Jira et al., 2001; Fitzky et al., 1998; Krakowiak et al., 2000). In one individual, this variant was observed in trans with a known pathogenic variant, p.Pro51Leu (Fitzky et al., 1998). Furthermore, RT-PCR and sequencing of the variant transcript showed that this variant leads to the use of an alternative splice acceptor in intron 8, which results in the insertion of 134 bp of intronic sequence, and ultimately a frameshift and premature termination (Fitzky et al., 1998). Loss of function is a mechanism of disease for this condition, however, no pathogenic nonsense or splice variants have been reported in DHCR7 downstream of this variant. This variant is reported at significantly higher frequency in affected individuals than the general population (OR=108.9000 (14.51-817.55)) (Witsch-Baumgartner et al., 2000). Multiple in silico algorithms predict this variant to be conserved and deleterious (CADD = 19.68; GERP=5.08). Emory Genetics Laboratory has classified this variant as Pathogenic, and The Genetic Services Laboratory of the University of Chicago has classified it as Likely Pathogenic. DHCR7 is the only gene in which variants have been shown to cause Smith-Lemli-Opitz Syndrome. Therefore, this collective evidence supports the classification of the c.964-1G>C as a Pathogenic variant for Smith-Lemli-Opitz Syndrome. We have confirmed this finding in our laboratory using Sanger sequencing. (less)
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Pathogenic
(Jan 30, 2015)
|
criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000281572.2
First in ClinVar: Jun 08, 2016 Last updated: Oct 09, 2016 |
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Pathogenic
(Jan 12, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000233039.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 31, 2019 |
Number of individuals with the variant: 36
Sex: mixed
|
|
Pathogenic
(Jun 22, 2018)
|
criteria provided, single submitter
Method: research
|
Smith-Lemli-Opitz syndrome
Affected status: yes
Allele origin:
paternal
|
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: CSER-SouthSeq
Accession: SCV000891754.1 First in ClinVar: Oct 10, 2018 Last updated: Oct 10, 2018 |
Comment:
ACMG codes: PVS1, PS3, PM2, PP5
Number of individuals with the variant: 1
Clinical Features:
Intrauterine growth retardation (present) , Oligohydramnios (present) , Long face (present) , High forehead (present) , Persistent open anterior fontanelle (present) , Short nose (present) … (more)
Intrauterine growth retardation (present) , Oligohydramnios (present) , Long face (present) , High forehead (present) , Persistent open anterior fontanelle (present) , Short nose (present) , Hypoplastic nasal tip (present) , Large earlobe (present) , Talipes equinovarus (present) , Wide intermamillary distance (present) , Pulmonic stenosis (present) , Partial agenesis of the corpus callosum (present) , Ventriculomegaly (present) , Renal dysplasia (present) , Optic nerve hypoplasia (present) , Thickened nuchal skin fold (present) , Congenital cataract (present) , Central hypotonia (present) , Polydactyly (present) , Hypoplastic nipples (present) , Small hand (present) , Foot polydactyly (present) (less)
|
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Pathogenic
(Mar 31, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
|
Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV001425360.1
First in ClinVar: Aug 02, 2020 Last updated: Aug 02, 2020 |
Comment:
DHCR7 c.964-1G>C is believed to be the most common disease-causing variant associated with Smith-Lemli-Opitz (SLO) syndrome and has been identified in affected individuals in both … (more)
DHCR7 c.964-1G>C is believed to be the most common disease-causing variant associated with Smith-Lemli-Opitz (SLO) syndrome and has been identified in affected individuals in both the homozygous and heterouzygous state. Five submitters in ClinVar classify this variant as either pathogenic or likely pathogenic. This DHCR7 variant (rs138659167) is present in a large population dataset (gnomAD: 1010/262084 total alleles; 0.3854%; no homozygotes) at a frequency that is consistent with the carrier frequency for SLO. We consider this variant to be pathogenic. (less)
|
|
Pathogenic
(Feb 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: yes
Allele origin:
germline
|
DASA
Accession: SCV002073776.1
First in ClinVar: Feb 12, 2022 Last updated: Feb 12, 2022 |
Comment:
The c.964-1G>C variant is located in a canonical splice-site, and it is not predicted the protein reading frame alteration, however, occur in a critical region … (more)
The c.964-1G>C variant is located in a canonical splice-site, and it is not predicted the protein reading frame alteration, however, occur in a critical region and the variant disrupts <10% of protein - PVS1_moderate. Well-established in vitro or in vivo functional studies support a damaging effect on the gene or gene product (PMID: 15805162) - PS3_moderate. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 93725, PMID: 22226660; 22211794; 23042628) - PS4. The c.964-1G>C was detected in trans with a pathogenic variant (PMID: 22226660) - PM3 and allele frequency is greater than expected for disorder - BS1. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 5
Sex: mixed
Geographic origin: Brazil, Uruguay
|
|
Pathogenic
(Jun 21, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
See cases
Affected status: yes
Allele origin:
germline
|
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Accession: SCV002522760.1
First in ClinVar: Jun 09, 2022 Last updated: Jun 09, 2022 |
Comment:
ACMG classification criteria: PVS1, PS3, PS4, PM3
Clinical Features:
Oligohydramnios (present) , Obesity (present) , Neurodevelopmental abnormality (present) , Hypotonia (present) , Attention deficit hyperactivity disorder (present) , Abnormality of mental function (present) , … (more)
Oligohydramnios (present) , Obesity (present) , Neurodevelopmental abnormality (present) , Hypotonia (present) , Attention deficit hyperactivity disorder (present) , Abnormality of mental function (present) , Oligohydramnios (present) , Obesity (present) , Neurodevelopmental abnormality (present) , Hypotonia (present) , Attention deficit hyperactivity disorder (present) , Abnormality of mental function (present) (less)
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|
Pathogenic
(Sep 02, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
(Autosomal recessive inheritance)
Affected status: no
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002767070.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Smith-Lemli-Opitz syndrome (MIM#270400). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Exceptionally mild and severe cases have been reported, with intrafamilial and interfamilial variable expressivity (PMID: 35305950, GeneReviews). (I) 0210 - Splice site variant proven to affect splicing of the transcript with a known effect on protein sequence. RNA studies have shown this variant results in a truncated protein with less than 1/3 of the protein affected (PMID: 9653161). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 1010 heterozygotes, 0 homozygotes). (SP) 0311 - An alternative nucleotide change at the same canonical splice site has been observed in gnomAD (v2: 17 heterozygotes, 0 homozygotes). (I) 0801 - This variant has very strong previous evidence of pathogenicity in unrelated individuals. It has been detected in multiple unrelated individuals with Smith-Lemli-Opitz syndrome, both homozygous and compound heterozygous (ClinVar, PMIDs: 9653161, 29455191) and is recognised as the most common pathogenic variant in this gene (GeneReviews). (SP) 1205 - This variant has been shown to be maternally inherited (by segregation analysis). The proband of this family has been analysed by an external laboratory. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
|
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Pathogenic
(Jul 28, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000611262.2
First in ClinVar: Apr 22, 2017 Last updated: Dec 31, 2022 |
|
|
Pathogenic
(Dec 06, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000321549.8
First in ClinVar: Oct 09, 2016 Last updated: Mar 04, 2023 |
Comment:
Considered to be the most common pathogenic variant associated with SLOS among Caucasian individuals from North America and Western Europe (Fitzky et al., 1998; DeBarber … (more)
Considered to be the most common pathogenic variant associated with SLOS among Caucasian individuals from North America and Western Europe (Fitzky et al., 1998; DeBarber et al., 2011); RT-PCR analysis revealed IVS8-1 G>C led to the use of an alternative SAS upstream from the mutated intron 8 splice site with the insertion of intron sequence, a shift of the reading frame, and premature stop (Fitzky et al., 1998); This variant is associated with the following publications: (PMID: 23293579, 26685159, 9653161, 10995508, 21777499, 33578785, 33204589, 32058062, 31589614, 31980526, 32055014, 32304219, 31618753, 31974414, 32257592, 31395954, 30925529, 9634533, 30947698, 11857552, 11298379, 29455191, 30609409, 28805615, 25533962, 28369852, 28250423, 12949967, 27065010, 25108116, 17965227, 25405082, 20556518, 22975760) (less)
|
|
Pathogenic
(Apr 19, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
unknown
|
Illumina Laboratory Services, Illumina
Accession: SCV000373914.3
First in ClinVar: Dec 06, 2016 Last updated: Jul 22, 2023 |
Comment:
The DHCR7 c.964-1G>C variant results in a substitution at the consensus splice acceptor site, which may result in splicing defects. The variant is well described … (more)
The DHCR7 c.964-1G>C variant results in a substitution at the consensus splice acceptor site, which may result in splicing defects. The variant is well described in the literature and is the most common pathogenic variant for Smith-Lemli-Opitz syndrome accounting for at least 29% of all disease alleles (PMID: 24824134). Across a selection of the available literature, the c.964-1G>C variant has been identified in over 80 patients, including at least 32 in a homozygous state and 49 in a compound heterozygous state (PMID: 9683613; 9653161; 10995508; 10814720; 11427181; 23293579; 32055014; 33204589). Individuals who are homozygous for the variant manifest a severe phenotype while compound heterozygotes have a more variable phenotype ranging from mild to severe (PMID: 32055014; 33204589). The highest frequency of this allele in the Genome Aggregation Database is 0.01182 in the Ashkenazi Jewish population (version 2.1.1). This frequency is high but is consistent with disease prevalence estimates. Functional analysis of the variant using RT-PCR in patient skin fibroblasts demonstrated that the variant causes aberrant mRNA splicing and insertion of 134 bp between exons 8 and 9 resulting in a frameshift that prematurely truncates the protein. The insertion occurs in a region strongly conserved among sterol reductases (PMID: 9683613). Based on the available evidence, the c.964-1G>C variant is classified as pathogenic for Smith-Lemli-Opitz syndrome. (less)
|
|
Pathogenic
(Nov 28, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004226618.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PS4, PVS1_strong
Number of individuals with the variant: 7
|
|
Pathogenic
(Feb 06, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004243396.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
|
|
Pathogenic
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000630077.9
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change affects an acceptor splice site in intron 8 of the DHCR7 gene. RNA analysis indicates that disruption of this splice site induces … (more)
This sequence change affects an acceptor splice site in intron 8 of the DHCR7 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely disrupts the C-terminus of the protein. This variant is present in population databases (rs138659167, gnomAD 1.2%), and has an allele count higher than expected for a pathogenic variant. Disruption of this splice site has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 10814720, 10995508, 11427181, 23042628). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 93725). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a new termination codon (PMID: 9653161). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Mar 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001245961.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Comment:
DHCR7: PM3:Strong, PM2, PP1, PP3, PP4, PS3:Supporting
Number of individuals with the variant: 15
|
|
Pathogenic
(May 06, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
unknown
|
Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV005042982.1
First in ClinVar: May 12, 2024 Last updated: May 12, 2024 |
Sex: male
Geographic origin: Iran
|
|
Pathogenic
(Jan 06, 2020)
|
no assertion criteria provided
Method: curation
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
|
Reproductive Health Research and Development, BGI Genomics
Accession: SCV001142422.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
Comment:
NG_012655.2(NM_001360.2):c.964-1G>C in the DHCR7 gene has an allele frequency of 0.012 in Ashkenazi Jewish subpopulation in the gnomAD database. The c.964-1G>C (IVS8-1G>C) is the most … (more)
NG_012655.2(NM_001360.2):c.964-1G>C in the DHCR7 gene has an allele frequency of 0.012 in Ashkenazi Jewish subpopulation in the gnomAD database. The c.964-1G>C (IVS8-1G>C) is the most common pathogenic variant for Smith-Lemli-Opitz syndrome accounting for at least 29% of all disease alleles (PMID: 24824134). Functional analysis of the variant using RT-PCR in patient with skin fibroblasts demonstrated that the variant causes aberrant mRNA splicing and insertion of 134 bp resulting in a frameshift that prematurely truncates the protein. The insertion occurs in a region strongly conserved among sterol reductases (PMID: 9683613). Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP Criteria applied: PVS1; PS4; PS3. (less)
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|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799020.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001806972.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001955116.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
Pathogenic
(Jul 23, 2015)
|
no assertion criteria provided
Method: research
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
|
Division of Human Genetics, Children's Hospital of Philadelphia
Study: CSER-PediSeq
Accession: SCV000536751.1 First in ClinVar: Apr 22, 2017 Last updated: Apr 22, 2017 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733106.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
Pathogenic
(Sep 16, 2018)
|
no assertion criteria provided
Method: research
|
not provided
Affected status: yes
Allele origin:
germline
|
Gharavi Laboratory, Columbia University
Accession: SCV000809236.1
First in ClinVar: Feb 15, 2018 Last updated: Feb 15, 2018 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Hadassah Hebrew University Medical Center
Accession: SCV000998809.1
First in ClinVar: Nov 24, 2019 Last updated: Nov 24, 2019 |
Comment:
known pathogenic variant: PMID 28805615, 22226660, 28369852, 12818773, 12914579, 29455191, 22929031 and others.
Clinical Features:
Elevated circulating 7-dehydrocholesterol concentration (present)
|
|
Pathogenic
(May 06, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: yes
Allele origin:
germline
|
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Accession: SCV001469217.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001550205.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The DHCR7 c.964-1G>C variant has been reported in over 70 cases of autosomal recessive Smith Lemli Opitz syndrome (SLOS) and is the most common variant … (more)
The DHCR7 c.964-1G>C variant has been reported in over 70 cases of autosomal recessive Smith Lemli Opitz syndrome (SLOS) and is the most common variant known to cause the disorder, accounting for ~28% of disease alleles (Nowaczyk_1998_PMID:20301322; Fitzky_1998_PMID:9653161; Krakowiak_2000_PMID:10995508; Witsch-Baumgartner_2001_PMID:11175299; DeBarber_2011_PMID:21777499). The variant was identified in dbSNP (ID: rs138659167) and ClinVar (classified as pathogenic by Laboratory for Molecular Medicine, Invitae and 21 other laboratories, and as likely pathogenic by Genetic Services Laboratory, University of Chicago and Equipe Genetique des Anomalies du Developpement, Université de Bourgogne). The variant was identified in control databases in 1010 of 262084 chromosomes (0 homozygous) at a frequency of 0.003854 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Ashkenazi Jewish in 116 of 9812 chromosomes (freq: 0.01182), European (non-Finnish) in 722 of 118782 chromosomes (freq: 0.006078), Other in 31 of 6836 chromosomes (freq: 0.004535), Latino in 67 of 34828 chromosomes (freq: 0.001924), African in 41 of 22690 chromosomes (freq: 0.001807), European (Finnish) in 30 of 19724 chromosomes (freq: 0.001521) and South Asian in 3 of 30116 chromosomes (freq: 0.0001), but was not observed in the East Asian population. The c.964-1G>C variant is predicted to cause abnormal splicing because the nucleotide substitution occurs in the invariant region of the splice consensus sequence. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict the loss of the canonical 3' splice site. Functional analysis has confirmed this aberrant splicing prediction and has revealed the use of an alternative splice acceptor site that produces a shifted reading frame and premature stop codon (Fitzky_1998_PMID:965316). Another functional study suggests that the c.964-1G>C variant disrupts SMO cilia localization and SHH pathway activation due to reduced cholesterol biosynthesis and reduced levels of the DHCR7 transcript (Blassberg_2016_PMID:26685159). In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
|
|
Pathogenic
(Mar 17, 2017)
|
no assertion criteria provided
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002093019.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect, ClinGen
Accession: SCV001423437.1
First in ClinVar: Jul 19, 2020 Last updated: Jul 19, 2020 |
Comment:
Variant interpretted as Pathogenic and reported on 06-04-2019 by Lab or GTR ID 1197. GenomeConnect assertions are reported exactly as they appear on the patient-provided … (more)
Variant interpretted as Pathogenic and reported on 06-04-2019 by Lab or GTR ID 1197. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Hyperthyroidism (present) , Depressivity (present) , Gingivitis (present)
Indication for testing: Carrier Screening
Age: 30-39 years
Sex: female
Testing laboratory: Myriad Genetic Laboratories, Inc.,Myriad Genetic Laboratories, Inc.
Date variant was reported to submitter: 2019-06-04
Testing laboratory interpretation: Pathogenic
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
|
GeneReviews
Accession: SCV000999075.2
First in ClinVar: Nov 24, 2019 Last updated: Oct 01, 2022 |
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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 |
---|---|---|---|---|
Extremely variable expressivity in Smith-Lemli-Opitz syndrome: Review of 4 cases. | Sánchez-Soler MJ | Anales de pediatria | 2022 | PMID: 35305950 |
Familial DHCR7 genotype presenting as a very mild form of Smith-Lemli-Opitz syndrome and lethal holoprosencephaly. | Temple SEL | JIMD reports | 2020 | PMID: 33204589 |
Smith-Lemli-Opitz syndrome: what is the actual risk for couples carriers of the DHCR7:c.964-1G>C variant? | Daum H | European journal of human genetics : EJHG | 2020 | PMID: 32055014 |
Smith-Lemli-Opitz Syndrome. | Adam MP | - | 2020 | PMID: 20301322 |
Smith-Lemli-Opitz syndrome: clinical and biochemical correlates. | Donoghue SE | Journal of pediatric endocrinology & metabolism : JPEM | 2018 | PMID: 29455191 |
Smith-Lemli-Opitz syndrome carrier frequency and estimates of in utero mortality rates. | Lazarin GA | Prenatal diagnosis | 2017 | PMID: 28166604 |
Identification of a large set of rare complete human knockouts. | Sulem P | Nature genetics | 2015 | PMID: 25807282 |
Birthday of a syndrome: 50 years anniversary of Smith-Lemli-Opitz Syndrome. | Witsch-Baumgartner M | European journal of human genetics : EJHG | 2015 | PMID: 24824134 |
Clinical utility of genetic testing in pediatric drug-resistant epilepsy: a pilot study. | Ream MA | Epilepsy & behavior : E&B | 2014 | PMID: 25108116 |
An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals. | Lazarin GA | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 22975760 |
Mutational spectrum of smith-lemli-opitz syndrome patients in hungary. | Balogh I | Molecular syndromology | 2012 | PMID: 23293579 |
Mutational spectrum of Smith-Lemli-Opitz syndrome. | Waterham HR | American journal of medical genetics. Part C, Seminars in medical genetics | 2012 | PMID: 23042628 |
Phenotypic spectrum of fetal Smith-Lemli-Opitz syndrome. | Quélin C | European journal of medical genetics | 2012 | PMID: 22226660 |
High frequency of p.Thr93Met in Smith-Lemli-Opitz syndrome patients in Turkey. | Kalb S | Clinical genetics | 2012 | PMID: 22211794 |
Smith-Lemli-Opitz syndrome. | DeBarber AE | Expert reviews in molecular medicine | 2011 | PMID: 21777499 |
Discordant phenotype and sterol biochemistry in Smith-Lemli-Opitz syndrome. | Koo G | American journal of medical genetics. Part A | 2010 | PMID: 20635399 |
A patient with Smith-Lemli-Opitz syndrome: novel mutation of the DHCR7 gene and effects of therapy with simvastatin and cholesterol supplement. | Szabó GP | European journal of pediatrics | 2010 | PMID: 19365639 |
Age and origin of major Smith-Lemli-Opitz syndrome (SLOS) mutations in European populations. | Witsch-Baumgartner M | Journal of medical genetics | 2008 | PMID: 17965227 |
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
DHCR7 mutation carrier rates and prevalence of the RSH/Smith-Lemli-Opitz syndrome: where are the patients? | Nowaczyk MJ | American journal of medical genetics. Part A | 2006 | PMID: 16906538 |
DHCR7 mutations in Brazilian Smith-Lemli-Opitz syndrome patients. | Scalco FB | American journal of medical genetics. Part A | 2005 | PMID: 15952211 |
DHCR7 nonsense mutations and characterisation of mRNA nonsense mediated decay in Smith-Lemli-Opitz syndrome. | Correa-Cerro LS | Journal of medical genetics | 2005 | PMID: 15805162 |
Identification of 14 novel mutations in DHCR7 causing the Smith-Lemli-Opitz syndrome and delineation of the DHCR7 mutational spectra in Spain and Italy. | Witsch-Baumgartner M | Human mutation | 2005 | PMID: 15776424 |
Carrier frequency of the RSH/Smith-Lemli-Opitz IVS8-1G>C mutation in African Americans. | Wright BS | American journal of medical genetics. Part A | 2003 | PMID: 12794707 |
Smith-Lemli-Opitz (RHS) syndrome: holoprosencephaly and homozygous IVS8-1G-->C genotype. | Nowaczyk MJ | American journal of medical genetics | 2001 | PMID: 11562938 |
Novel mutations in the 7-dehydrocholesterol reductase gene of 13 patients with Smith--Lemli--Opitz syndrome. | Jira PE | Annals of human genetics | 2001 | PMID: 11427181 |
Mutations in the human DHCR7 gene. | Witsch-Baumgartner M | Human mutation | 2001 | PMID: 11241839 |
Frequency gradients of DHCR7 mutations in patients with Smith-Lemli-Opitz syndrome in Europe: evidence for different origins of common mutations. | Witsch-Baumgartner M | European journal of human genetics : EJHG | 2001 | PMID: 11175299 |
Carrier frequency of the common mutation IVS8-1G>C in DHCR7 and estimate of the expected incidence of Smith-Lemli-Opitz syndrome. | Battaile KP | Molecular genetics and metabolism | 2001 | PMID: 11161831 |
Mutation analysis and description of sixteen RSH/Smith-Lemli-Opitz syndrome patients: polymerase chain reaction-based assays to simplify genotyping. | Krakowiak PA | American journal of medical genetics | 2000 | PMID: 10995508 |
Spectrum of Delta(7)-dehydrocholesterol reductase mutations in patients with the Smith-Lemli-Opitz (RSH) syndrome. | Yu H | Human molecular genetics | 2000 | PMID: 10814720 |
Mutational spectrum in the Delta7-sterol reductase gene and genotype-phenotype correlation in 84 patients with Smith-Lemli-Opitz syndrome. | Witsch-Baumgartner M | American journal of human genetics | 2000 | PMID: 10677299 |
Smith-Lemli-Opitz syndrome is caused by mutations in the 7-dehydrocholesterol reductase gene. | Waterham HR | American journal of human genetics | 1998 | PMID: 9683613 |
Mutations in the Delta7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome. | Fitzky BU | Proceedings of the National Academy of Sciences of the United States of America | 1998 | PMID: 9653161 |
Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
Smith-Lemli-Opitz syndrome: treatment with cholesterol and bile acids. | Ullrich K | Neuropediatrics | 1996 | PMID: 8737829 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DHCR7 | - | - | - | - |
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Text-mined citations for rs138659167 ...
HelpRecord last updated May 27, 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.