ClinVar Miner

Submissions for variant NM_001360.3(DHCR7):c.111G>A (p.Trp37Ter)

gnomAD frequency: 0.00003  dbSNP: rs750345068
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169596 SCV000221107 likely pathogenic Smith-Lemli-Opitz syndrome 2015-01-30 criteria provided, single submitter literature only
Labcorp Genetics (formerly Invitae), Labcorp RCV000169596 SCV002230889 pathogenic Smith-Lemli-Opitz syndrome 2024-02-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp37*) in the DHCR7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DHCR7 are known to be pathogenic (PMID: 9634533, 10677299). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with clinical features of Smith–Lemli–Opitz syndrome (PMID: 10814720). ClinVar contains an entry for this variant (Variation ID: 189168). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169596 SCV002500115 likely pathogenic Smith-Lemli-Opitz syndrome 2022-03-05 criteria provided, single submitter clinical testing Variant summary: DHCR7 c.111G>A (p.Trp37X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.9e-05 in 210516 control chromosomes. c.111G>A has been reported in the literature with an ambiguous annotation as E37X without a second reported allele in at-least one individual affected with Smith-Lemli-Opitz Syndrome (example, Yu_2000). 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. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000169596 SCV002801120 pathogenic Smith-Lemli-Opitz syndrome 2021-07-07 criteria provided, single submitter clinical testing
OMIM RCV000169596 SCV000027384 pathogenic Smith-Lemli-Opitz syndrome 2000-05-22 no assertion criteria provided literature only

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