Submissions for variant NM_001360.3(DHCR7):c.1341C>T (p.Asp447=)

gnomAD frequency: 0.00296  dbSNP: rs139721775

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079642	SCV000111525	benign	not specified	2013-04-16	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003891551	SCV000307640	benign	DHCR7-related disorder	2023-11-07	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
CeGaT Center for Human Genetics Tuebingen	RCV000512660	SCV000608603	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	DHCR7: BP4, BP7, BS2
Invitae	RCV001084025	SCV000630072	benign	Smith-Lemli-Opitz syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000512660	SCV000697852	likely benign	not provided	2017-05-02	criteria provided, single submitter	clinical testing	Variant summary: The DHCR7 c.1341C>T (p.Asp447Asp) variant involves the alteration of a non-conserved nucleotide causing a synonymous change and 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may eliminate ESE binding sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 399/117638 control chromosomes (6 homozygotes) at a frequency of 0.0033918, which does not exceed the estimated maximal expected allele frequency of a pathogenic DHCR7 variant (0.0043301).Review publications, Jira_2003 and Wareham_2000, classify the variant as a "polymorphism," along with a publication indicating the variant to have been found in a cohort of SLOS patients and classified it as "polymorphism," as well as suggesting the variant may have co-occurred with a deleterious DHCR7 variant. In addition, multiple clinical diagnostic laboratories classified this variant as "likely benign/benign." Taken together, this variant is classified as "likely benign."
Ambry Genetics	RCV002311593	SCV000846972	likely benign	Inborn genetic diseases	2016-06-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000512660	SCV000883710	benign	not provided	2018-01-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001084025	SCV001270466	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx	RCV000512660	SCV001870577	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28972118)
Genetic Services Laboratory, University of Chicago	RCV000079642	SCV002069428	benign	not specified	2019-03-29	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001084025	SCV002794941	likely benign	Smith-Lemli-Opitz syndrome	2021-08-21	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000079642	SCV001978043	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000512660	SCV001980498	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001084025	SCV002092995	likely benign	Smith-Lemli-Opitz syndrome	2017-03-28	no assertion criteria provided	clinical testing