ClinVar Genomic variation as it relates to human health
NM_001360.3(DHCR7):c.111G>A (p.Trp37Ter)
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
-
NM_001360.3(DHCR7):c.111G>A (p.Trp37Ter)
Variation ID: 189168 Accession: VCV000189168.10
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 11q13.4 11: 71444203 (GRCh38) [ NCBI UCSC ] 11: 71155249 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Feb 14, 2024 Nov 24, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001360.3:c.111G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001351.2:p.Trp37Ter nonsense NM_001163817.2:c.111G>A NP_001157289.1:p.Trp37Ter nonsense NC_000011.10:g.71444203C>T NC_000011.9:g.71155249C>T NG_012655.2:g.9229G>A LRG_340:g.9229G>A LRG_340t1:c.111G>A LRG_340p1:p.Trp37Ter - Protein change
- W37*
- Other names
- -
- Canonical SPDI
- NC_000011.10:71444202:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
Exome Aggregation Consortium (ExAC) 0.00006
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 | ||
---|---|---|---|---|---|---|
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. |
|||
DHCR7 | - | - |
GRCh38 GRCh37 |
- | 927 |
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 (5) |
criteria provided, multiple submitters, no conflicts
|
Nov 24, 2023 | RCV000169596.10 |
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. |
|
---|---|---|---|---|---|
Likely pathogenic
(Jan 30, 2015)
|
criteria provided, single submitter
Method: literature only
|
Smith-Lemli-Opitz syndrome
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000221107.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
|
|
Likely pathogenic
(Mar 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002500115.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Comment:
Variant summary: DHCR7 c.111G>A (p.Trp37X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: DHCR7 c.111G>A (p.Trp37X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.9e-05 in 210516 control chromosomes. c.111G>A has been reported in the literature with an ambiguous annotation as E37X without a second reported allele in at-least one individual affected with Smith-Lemli-Opitz Syndrome (example, Yu_2000). These report(s) do not provide unequivocal conclusions about association of the variant with Smith-Lemli-Opitz Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
|
|
Pathogenic
(Jul 07, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002801120.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Pathogenic
(Nov 24, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002230889.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Trp37*) in the DHCR7 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Trp37*) in the DHCR7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DHCR7 are known to be pathogenic (PMID: 9634533, 10677299). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with clinical features of Smith–Lemli–Opitz syndrome (PMID: 10814720). ClinVar contains an entry for this variant (Variation ID: 189168). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(May 22, 2000)
|
no assertion criteria provided
Method: literature only
|
SMITH-LEMLI-OPITZ SYNDROME
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000027384.2
First in ClinVar: Apr 04, 2013 Last updated: Mar 24, 2015 |
Comment on evidence:
Among 32 patients with Smith-Lemli-Opitz syndrome (SLOS; 270400), Yu et al. (2000) found 1 patient with a G-to-A transition in exon 4 in one allele … (more)
Among 32 patients with Smith-Lemli-Opitz syndrome (SLOS; 270400), Yu et al. (2000) found 1 patient with a G-to-A transition in exon 4 in one allele of the DHCR7 gene, resulting in a trp37-to-ter substitution (W37X). (less)
|
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 |
---|---|---|---|---|
Increased nonsterol isoprenoids, dolichol and ubiquinone, in the Smith-Lemli-Opitz syndrome: effects of dietary cholesterol. | Pappu AS | Journal of lipid research | 2006 | PMID: 16983147 |
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 |
Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome. | Wassif CA | American journal of human genetics | 1998 | PMID: 9634533 |
Text-mined citations for rs750345068 ...
HelpRecord last updated Feb 20, 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.