ClinVar Genomic variation as it relates to human health
NM_001360.3(DHCR7):c.440G>A (p.Gly147Asp)
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.440G>A (p.Gly147Asp)
Variation ID: 381657 Accession: VCV000381657.20
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.4 11: 71441413 (GRCh38) [ NCBI UCSC ] 11: 71152459 (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 Mar 8, 2017 Feb 14, 2024 Jan 16, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001360.3:c.440G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001351.2:p.Gly147Asp missense NM_001163817.2:c.440G>A NP_001157289.1:p.Gly147Asp missense NC_000011.10:g.71441413C>T NC_000011.9:g.71152459C>T NG_012655.2:g.12019G>A LRG_340:g.12019G>A LRG_340t1:c.440G>A LRG_340p1:p.Gly147Asp - Protein change
- G147D
- Other names
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- Canonical SPDI
- NC_000011.10:71441412:C:T
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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.
Exome Aggregation Consortium (ExAC) 0.00007
Trans-Omics for Precision Medicine (TOPMed) 0.00008
The Genome Aggregation Database (gnomAD) 0.00009
The Genome Aggregation Database (gnomAD), exomes 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
Help
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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DHCR7 | - | - |
GRCh38 GRCh37 |
935 | 950 |
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
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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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Likely pathogenic (1) |
criteria provided, single submitter
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Jun 7, 2023 | RCV000421810.5 | |
Pathogenic/Likely pathogenic (7) |
criteria provided, multiple submitters, no conflicts
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Jan 16, 2024 | RCV000665794.18 |
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
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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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Likely pathogenic
(Mar 21, 2017)
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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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Counsyl
Accession: SCV000789970.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Pathogenic
(-)
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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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Baylor Genetics
Accession: SCV001163338.1
First in ClinVar: Feb 29, 2020 Last updated: Feb 29, 2020 |
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Pathogenic
(Dec 23, 2020)
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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: SCV001361500.2
First in ClinVar: Jun 22, 2020 Last updated: Jan 05, 2021 |
Comment:
Variant summary: DHCR7 c.440G>A (p.Gly147Asp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Variant summary: DHCR7 c.440G>A (p.Gly147Asp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.8e-05 in 248932 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in DHCR7 causing Smith-Lemli-Opitz Syndrome (8.8e-05 vs 0.0043), allowing no conclusion about variant significance. c.440G>A has been reported in the literature in multiple individuals affected with Smith-Lemli-Opitz Syndrome (e.g. Witsch-Baumgartner_2000, Krakowiak_2000, Goldenberg_2003, Petracchi_2011). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Likely pathogenic
(Jan 19, 2022)
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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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Fulgent Genetics, Fulgent Genetics
Accession: SCV002790135.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Likely pathogenic
(Jun 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000521158.7
First in ClinVar: Mar 08, 2017 Last updated: Jun 17, 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: 21706511, … (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: 21706511, 10995508, 28250423, 10677299, 31980526, 29770994, 12818773, 27401223, 15896653) (less)
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Likely pathogenic
(Mar 13, 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:
germline
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Revvity Omics, Revvity
Accession: SCV002024075.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 16, 2024)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000946087.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 147 of the DHCR7 protein … (more)
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 147 of the DHCR7 protein (p.Gly147Asp). This variant is present in population databases (rs777425801, gnomAD 0.02%). This missense change has been observed in individuals with Smith–Lemli–Opitz syndrome (PMID: 10995508, 12818773). ClinVar contains an entry for this variant (Variation ID: 381657). 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 DHCR7 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001460495.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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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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Holoprosencephaly at prenatal diagnosis: analysis of 28 cases regarding etiopathogenic diagnoses. | Petracchi F | Prenatal diagnosis | 2011 | PMID: 21706511 |
Residual cholesterol synthesis and simvastatin induction of cholesterol synthesis in Smith-Lemli-Opitz syndrome fibroblasts. | Wassif CA | Molecular genetics and metabolism | 2005 | PMID: 15896653 |
[Clinical characteristics and diagnosis of Smith-Lemli-Opitz syndrome and tentative phenotype-genotype correlation: report of 45 cases]. | Goldenberg A | Archives de pediatrie : organe officiel de la Societe francaise de pediatrie | 2003 | PMID: 12818773 |
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 |
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 |
Text-mined citations for rs777425801 ...
HelpRecord last updated Sep 29, 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.