ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.839A>G (p.Tyr280Cys) (rs121909766)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000007192 SCV001221466 likely pathogenic Smith-Lemli-Opitz syndrome 2019-05-07 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 280 of the DHCR7 protein (p.Tyr280Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another DHCR7 variant in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 11857552). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 6790). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000007192 SCV000027388 pathogenic Smith-Lemli-Opitz syndrome 2002-02-15 no assertion criteria provided literature only

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