ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.655T>G (p.Tyr219Asp) (rs779896782)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668765 SCV000793417 uncertain significance Smith-Lemli-Opitz syndrome 2017-08-16 criteria provided, single submitter clinical testing
GeneDx RCV000493359 SCV000582971 likely pathogenic not provided 2015-12-10 criteria provided, single submitter clinical testing The Y219D variant in the DHCR7 gene has been reported previously in an individual with Smith-Lemli-Opitz syndrome in the compound heterozygous state with another pathogenic variant (Jezela-Stanek et al., 2008). The Y219D variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Y219D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Although this substitution occurs at a position that is not conserved, in silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in a nearby residue (E224K) has been reported in association with Smith-Lemli-Opitz syndrome (Witsch-Baumgartner et al., 2005), supporting the functional importance of this region of the protein. The Y219D variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.

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