ClinVar Genomic variation as it relates to human health
NM_001360.3(DHCR7):c.730G>A (p.Gly244Arg)
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001360.3(DHCR7):c.730G>A (p.Gly244Arg)
Variation ID: 6781 Accession: VCV000006781.28
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.4 11: 71438980 (GRCh38) [ NCBI UCSC ] 11: 71150026 (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 24, 2015 Apr 20, 2025 Jun 17, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001360.3:c.730G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001351.2:p.Gly244Arg missense NM_001163817.2:c.730G>A NP_001157289.1:p.Gly244Arg missense NC_000011.10:g.71438980C>T NC_000011.9:g.71150026C>T NG_012655.2:g.14452G>A LRG_340:g.14452G>A LRG_340t1:c.730G>A LRG_340p1:p.Gly244Arg Q9UBM7:p.Gly244Arg - Protein change
- G244R
- Other names
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- Canonical SPDI
- NC_000011.10:71438979: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
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The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD) 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00004
Exome Aggregation Consortium (ExAC) 0.00005
1000 Genomes Project 30x 0.00031
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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| HI score
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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 | Gene associated with autosomal recessive phenotype | No evidence available |
GRCh38 GRCh37 |
998 | 1013 | |
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. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Jun 17, 2024 | RCV000007183.18 | |
| Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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May 1, 2024 | RCV001804715.15 | |
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DHCR7-related disorder
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Pathogenic (1) |
no assertion criteria provided
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May 16, 2024 | RCV004748505.1 |
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
(-)
C
Contributing to aggregate classification
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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: SCV001163701.1
First in ClinVar: Feb 28, 2020 Last updated: Feb 28, 2020 |
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Likely pathogenic
(Jan 03, 2022)
C
Contributing to aggregate classification
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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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3billion
Accession: SCV002059016.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000006781, PMID:9683613, PS1_S). In … (more)
Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000006781, PMID:9683613, PS1_S). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.972, 3CNET: 0.993, PP3_P). A missense variant is a common mechanism associated with Smith-Lemli-Opitz syndrome (PP2_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000032, PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Abnormality of the dentition (present) , Highly arched eyebrow (present) , Intellectual disability (present) , Microcephaly (present) , Periorbital fullness (present) , Macrodontia of permanent maxillary central incisor (present) , Retrognathia (present) , Smooth philtrum (present) , Thin upper lip vermilion (present) , Wide mouth (present)
Zygosity: Single Heterozygote
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Likely pathogenic
(Mar 16, 2021)
C
Contributing to aggregate classification
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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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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV002051646.2
First in ClinVar: Jan 08, 2022 Last updated: Feb 12, 2022 |
Comment:
PS3, PS4_Moderate
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Pathogenic
(Dec 15, 2023)
C
Contributing to aggregate classification
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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: SCV000941238.5
First in ClinVar: Aug 14, 2019 Last updated: Feb 25, 2025 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 244 of the DHCR7 protein (p.Gly244Arg). … (more)
This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 244 of the DHCR7 protein (p.Gly244Arg). This variant is present in population databases (rs121909764, gnomAD 0.02%). This missense change has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 9683613, 12270273, 12818773, 23293579). ClinVar contains an entry for this variant (Variation ID: 6781). 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
(Jun 17, 2024)
C
Contributing to aggregate classification
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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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Fulgent Genetics, Fulgent Genetics
Accession: SCV005629862.1
First in ClinVar: Jan 25, 2025 Last updated: Jan 25, 2025 |
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Likely pathogenic
(May 01, 2024)
C
Contributing to aggregate classification
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004701139.11
First in ClinVar: Mar 10, 2024 Last updated: Apr 20, 2025 |
Comment:
DHCR7: PM3:Strong, PM2, PP3
Number of individuals with the variant: 2
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Pathogenic
(Aug 01, 1998)
N
Not contributing to aggregate classification
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no assertion criteria provided
Method: literature only
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SMITH-LEMLI-OPITZ SYNDROME
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000027379.3
First in ClinVar: Apr 04, 2013 Last updated: Mar 24, 2015 |
Comment on evidence:
For discussion of the gly244-to-arg (G244R) mutation in the DHCR7 gene that was found in compound heterozygous state in a patient with Smith-Lemli-Opitz syndrome (SLOS; … (more)
For discussion of the gly244-to-arg (G244R) mutation in the DHCR7 gene that was found in compound heterozygous state in a patient with Smith-Lemli-Opitz syndrome (SLOS; 270400) by Waterham et al. (1998), see 602858.0005. (less)
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Pathogenic
(Dec 28, 2020)
N
Not contributing to aggregate classification
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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: SCV002093030.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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Pathogenic
(May 16, 2024)
N
Not contributing to aggregate classification
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no assertion criteria provided
Method: clinical testing
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DHCR7-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV005361263.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The DHCR7 c.730G>A variant is predicted to result in the amino acid substitution p.Gly244Arg. This variant has been reported in the compound heterozygous state in … (more)
The DHCR7 c.730G>A variant is predicted to result in the amino acid substitution p.Gly244Arg. This variant has been reported in the compound heterozygous state in several individuals with Smith-Lemli-Opitz syndrome (Waterham et al. 1998. PubMed ID: 9683613; Balogh et al. 2012. PubMed ID: 23293579; Korade et al. 2017. PubMed ID: 28972118). This variant is reported in 0.020% of alleles in individuals of South Asian descent in gnomAD. This variant is interpreted as pathogenic. (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
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Mutational spectrum of smith-lemli-opitz syndrome patients in hungary. | Balogh I | Molecular syndromology | 2012 | PMID: 23293579 |
| [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 |
| Two novel mutations of the human delta7-sterol reductase (DHCR7) gene in children with Smith-Lemli-Opitz syndrome. | Patrono C | Molecular and cellular probes | 2002 | PMID: 12270273 |
| Smith-Lemli-Opitz syndrome is caused by mutations in the 7-dehydrocholesterol reductase gene. | Waterham HR | American journal of human genetics | 1998 | PMID: 9683613 |
Text-mined citations for rs121909764 ...
HelpRecord last updated May 17, 2025
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.