Submissions for variant NM_001360.3(DHCR7):c.1008C>T (p.His336=)

gnomAD frequency: 0.00447  dbSNP: rs75225632

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000153141	SCV000202602	benign	not specified	2014-02-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000328864	SCV000373912	likely benign	Smith-Lemli-Opitz syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000328864	SCV000630070	benign	Smith-Lemli-Opitz syndrome	2025-02-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589158	SCV000697849	benign	not provided	2017-03-27	criteria provided, single submitter	clinical testing	Variant summary: The DHCR7 c.1008C>T (p.His336His) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 889/113020 control chromosomes from ExAC (including 28 homozygotes), predominantly observed in the East Asian subpopulation at a frequency of 0.066619 (558/8376). This frequency is about 15 times the estimated maximal expected allele frequency of a pathogenic DHCR7 variant (0.0043301), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. At least one clinical diagnostic laboratory in ClinVar has classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as Benign.
Ambry Genetics	RCV002312675	SCV000846987	benign	Inborn genetic diseases	2016-05-06	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.
Genome-Nilou Lab	RCV000328864	SCV001737360	benign	Smith-Lemli-Opitz syndrome	2021-06-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000589158	SCV001830031	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000328864	SCV002048931	benign	Smith-Lemli-Opitz syndrome	2021-03-16	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000589158	SCV005218394	likely benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV000328864	SCV002093016	benign	Smith-Lemli-Opitz syndrome	2017-05-05	no assertion criteria provided	clinical testing