ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.199G>A (p.Ala67Thr) (rs143999854)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000681711 SCV000111531 uncertain significance not provided 2018-06-05 criteria provided, single submitter clinical testing
GeneDx RCV000079648 SCV000729508 likely benign not specified 2017-06-23 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Counsyl RCV000509217 SCV000799918 uncertain significance Smith-Lemli-Opitz syndrome 2018-05-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000717461 SCV000848313 uncertain significance History of neurodevelopmental disorder 2019-08-30 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000509217 SCV000933283 uncertain significance Smith-Lemli-Opitz syndrome 2019-11-04 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 67 of the DHCR7 protein (p.Ala67Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs143999854, ExAC 0.1%). This variant has not been reported in the literature in individuals with DHCR7-related disease. ClinVar contains an entry for this variant (Variation ID: 93714). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Illumina Clinical Services Laboratory,Illumina RCV000509217 SCV001270545 uncertain significance Smith-Lemli-Opitz syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GenomeConnect, ClinGen RCV000681711 SCV000606908 not provided not provided no assertion provided phenotyping only Variant interpretted as Likely Benign and reported on 11-13-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Gharavi Laboratory,Columbia University RCV000681711 SCV000809164 likely pathogenic not provided 2018-09-16 no assertion criteria provided research

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