ClinVar Miner

Submissions for variant NM_001360.3(DHCR7):c.1218C>G (p.Phe406Leu)

dbSNP: rs1949268068
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001207177 SCV001378518 uncertain significance Smith-Lemli-Opitz syndrome 2022-03-20 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 406 of the DHCR7 protein (p.Phe406Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DHCR7-related conditions. ClinVar contains an entry for this variant (Variation ID: 938032). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genetic Services Laboratory, University of Chicago RCV001819896 SCV002065766 uncertain significance not specified 2021-12-10 criteria provided, single submitter clinical testing DNA sequence analysis of the DHCR7 gene demonstrated a sequence change, c.1218C>G, in exon 9 that results in an amino acid change, p.Phe406Leu. This sequence change does not appear to have been previously described in individuals with DHCR7-related disorders and has also not been described in the population databases such as ExAC and gnomAD. The p.Phe406Leu change affects a moderately conserved amino acid residue located in a domain of the DHCR7 protein that is known to be functional. The p.Phe406Leu substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Phe406Leu change remains unknown at this time.
Fulgent Genetics, Fulgent Genetics RCV001207177 SCV002776282 uncertain significance Smith-Lemli-Opitz syndrome 2022-03-30 criteria provided, single submitter clinical testing
GeneDx RCV002509629 SCV002819132 uncertain significance not provided 2022-07-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001207177 SCV002093002 uncertain significance Smith-Lemli-Opitz syndrome 2019-04-22 no assertion criteria provided clinical testing

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