ClinVar Miner

Submissions for variant NM_001360.3(DHCR7):c.321G>C (p.Gln107His)

gnomAD frequency: 0.00002  dbSNP: rs104886040
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001004377 SCV001163341 likely pathogenic Smith-Lemli-Opitz syndrome criteria provided, single submitter clinical testing
Invitae RCV001004377 SCV003011042 uncertain significance Smith-Lemli-Opitz syndrome 2022-06-10 criteria provided, single submitter clinical testing This sequence change affects codon 107 of the DHCR7 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the DHCR7 protein. RNA analysis indicates that this variant induces altered splicing and likely results in the gain of 12 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is present in population databases (rs104886040, gnomAD 0.01%). This variant has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 15896653). ClinVar contains an entry for this variant (Variation ID: 813426). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in the activation of a cryptic splice site in intron 4 (PMID: 10995508). 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.

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