ClinVar Genomic variation as it relates to human health
NM_001360.3(DHCR7):c.1348del (p.Arg450fs)
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.1348del (p.Arg450fs)
Variation ID: 282268 Accession: VCV000282268.19
- Type and length
-
Deletion, 1 bp
- Location
-
Cytogenetic: 11q13.4 11: 71435455 (GRCh38) [ NCBI UCSC ] 11: 71146501 (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 Dec 6, 2016 Feb 14, 2024 Dec 15, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001360.3:c.1348del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001351.2:p.Arg450fs frameshift NM_001163817.2:c.1348del NP_001157289.1:p.Arg450fs frameshift NM_001360.2:c.1348del NM_001360.2:c.1348delC NC_000011.10:g.71435456del NC_000011.9:g.71146502del NG_012655.2:g.17977del LRG_340:g.17977del - Protein change
- R450fs
- Other names
- -
- Canonical SPDI
- NC_000011.10:71435454:GG:G
-
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.
-
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 |
912 | 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
|
Dec 15, 2023 | RCV000316051.12 | |
Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 1, 2023 | RCV000725059.8 |
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
(Aug 11, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000333636.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
Likely pathogenic
(Apr 01, 2021)
|
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: SCV001572441.1
First in ClinVar: Apr 30, 2021 Last updated: Apr 30, 2021 |
Comment:
Variant summary: DHCR7 c.1348delC (p.Arg450AlafsX31) located in the last exon (exon 9) causes a frameshift which results in an extension of the protein. The variant … (more)
Variant summary: DHCR7 c.1348delC (p.Arg450AlafsX31) located in the last exon (exon 9) causes a frameshift which results in an extension of the protein. The variant was absent in 248600 control chromosomes. c.1348delC has been reported in the literature in one heterozygous individual who had a near normal ratio of fractional choloesterol synthesis (Wassif_2005). 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. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
|
|
Likely pathogenic
(Feb 10, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002813917.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Likely pathogenic
(Nov 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001784580.3
First in ClinVar: Aug 14, 2021 Last updated: Nov 25, 2023 |
Comment:
Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 26 amino acids are lost and replaced with 30 incorrect amino … (more)
Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 26 amino acids are lost and replaced with 30 incorrect amino acids; Not observed in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge (less)
|
|
Pathogenic
(Dec 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001576443.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change results in a frameshift in the DHCR7 gene (p.Arg450Alafs*31). While this is not anticipated to result in nonsense mediated decay, it is … (more)
This sequence change results in a frameshift in the DHCR7 gene (p.Arg450Alafs*31). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 26 amino acid(s) of the DHCR7 protein and extend the protein by 4 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DHCR7-related conditions. ClinVar contains an entry for this variant (Variation ID: 282268). This variant disrupts a region of the DHCR7 protein in which other variant(s) (p.Arg450Leu) have been determined to be pathogenic (PMID: 10405455, 15896653, 16181459, 22391996, 25405082). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Uncertain significance
(Apr 20, 2018)
|
no assertion criteria provided
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000800696.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
|
|
Likely pathogenic
(Dec 23, 2019)
|
no assertion criteria provided
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002092993.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
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 |
---|---|---|---|---|
Elevated Autophagy and Mitochondrial Dysfunction in the Smith-Lemli-Opitz Syndrome. | Chang S | Molecular genetics and metabolism reports | 2014 | PMID: 25405082 |
No evidence for mevalonate shunting in moderately affected children with Smith-Lemli-Opitz syndrome. | Roullet JB | Journal of inherited metabolic disease | 2012 | PMID: 22391996 |
Photosensitive Smith-Lemli-Opitz syndrome is not caused by a single gene mutation: analysis of the gene encoding 7-dehydrocholesterol reductase in five U.K. families. | Anstey AV | The British journal of dermatology | 2005 | PMID: 16181459 |
Residual cholesterol synthesis and simvastatin induction of cholesterol synthesis in Smith-Lemli-Opitz syndrome fibroblasts. | Wassif CA | Molecular genetics and metabolism | 2005 | PMID: 15896653 |
Biochemical variants of Smith-Lemli-Opitz syndrome. | Neklason DW | American journal of medical genetics | 1999 | PMID: 10405455 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DHCR7 | - | - | - | - |
Text-mined citations for rs886042362 ...
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.