ClinVar Miner

Submissions for variant NM_001360.3(DHCR7):c.139C>T (p.Leu47=)

gnomAD frequency: 0.00027  dbSNP: rs140721259
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000279800 SCV000335785 uncertain significance not provided 2015-10-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV002314006 SCV000848849 likely benign Inborn genetic diseases 2017-01-17 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.
Invitae RCV001483712 SCV001688114 likely benign Smith-Lemli-Opitz syndrome 2024-01-25 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.
GeneDx RCV000279800 SCV001981889 likely benign not provided 2021-01-18 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003909950 SCV004725990 likely benign DHCR7-related disorder 2021-06-14 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Natera, Inc. RCV001483712 SCV002093076 likely benign Smith-Lemli-Opitz syndrome 2020-11-02 no assertion criteria provided clinical testing

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