ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.570C>T (p.Ala190=) (rs74909468)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000390465 SCV000373919 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.
GeneDx RCV000428094 SCV000512801 benign not specified 2016-01-04 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000390465 SCV000754775 benign Smith-Lemli-Opitz syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000716503 SCV000847344 benign History of neurodevelopmental disorder 2016-03-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000428094 SCV000919260 likely benign not specified 2017-09-11 criteria provided, single submitter clinical testing Variant summary: The DHCR7 c.570C>T (p.Ala190Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging 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. The variant was found in the control population dataset of ExAC in 389/121388 control chromosomes (5 homozygotes) at a frequency of 0.0032046 and in gnomAD in 941/276256 control chromosomes (15 homozygotes) at a frequency of 0.003406, which do not exceed the estimated maximal expected allele frequency of a pathogenic DHCR7 variant (0.0043301). One clinical diagnostic laboratory classified this variant as uncertain significance and a second one classified it as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000390465 SCV001159636 benign Smith-Lemli-Opitz syndrome 2018-10-29 criteria provided, single submitter clinical testing

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