Submissions for variant NM_001360.3(DHCR7):c.99-4G>A

gnomAD frequency: 0.00988  dbSNP: rs140748737

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079662	SCV000111545	benign	not specified	2013-04-16	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000428279	SCV000511366	likely benign	not provided	2016-09-14	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000538327	SCV000630079	benign	Smith-Lemli-Opitz syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000428279	SCV000697861	benign	not provided	2017-05-02	criteria provided, single submitter	clinical testing	Variant summary: The DHCR7 c.99-4G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 628/37018 control chromosomes (8 homozygotes) at a frequency of 0.0169647, which is approximately 4 times the estimated maximal expected allele frequency of a pathogenic DHCR7 variant (0.0043301), suggesting this variant is likely a benign polymorphism. The variant of interest has been reported in affected individuals without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
Ambry Genetics	RCV002311598	SCV000846362	benign	Inborn genetic diseases	2016-03-13	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	RCV000079662	SCV000864293	likely benign	not specified	2017-07-05	criteria provided, single submitter	clinical testing	BS1, BP6; This alteration has an allele frequency that is greater than expected for the associated disease, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory).
Mendelics	RCV000428279	SCV001135034	benign	not provided	2019-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000538327	SCV001157157	benign	Smith-Lemli-Opitz syndrome	2020-02-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000538327	SCV001272046	likely benign	Smith-Lemli-Opitz syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx	RCV000428279	SCV001848422	benign	not provided	2018-12-17	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25040602, 23042628)
CeGaT Center for Human Genetics Tuebingen	RCV000428279	SCV002585336	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	DHCR7: BP4, BS1, BS2
Natera, Inc.	RCV000538327	SCV001190684	benign	Smith-Lemli-Opitz syndrome	2019-05-20	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000428279	SCV001797508	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000428279	SCV001929097	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000079662	SCV001976137	benign	not specified		no assertion criteria provided	clinical testing