ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.139C>T (p.Leu47=) (rs140721259)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000279800 SCV000335785 uncertain significance not provided 2015-10-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV000717988 SCV000848849 likely benign History of neurodevelopmental disorder 2017-01-17 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Invitae RCV001483712 SCV001688114 likely benign Smith-Lemli-Opitz syndrome 2020-05-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001532990 SCV001748825 likely benign not specified 2021-06-23 criteria provided, single submitter clinical testing Variant summary: DHCR7 c.139C>T alters a conserved nucleotide resulting in a synonymous change. 4/4 computational tools predict no significant impact on normal splicing while predicting the disruption of ESE binding sites. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 5.9e-05 in 236214 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in DHCR7 causing Smith-Lemli-Opitz Syndrome (5.9e-05 vs 0.0043), allowing no conclusion about variant significance. c.139C>T has been reported in the literature as a polymorphism and/or non pathogenic variant in individuals affected with Smith-Lemli-Opitz Syndrome (example, Witsch-Baumgartner_2001, Jira_2003, Waterham_2012). 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. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (VUS, n=1; likely benign, n=2). Based on the evidence outlined above, the variant was classified as likely benign.

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