Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000003340 | SCV000915806 | uncertain significance | Smith-McCort dysplasia 1 | 2018-10-29 | criteria provided, single submitter | clinical testing | The DYM c.259G>A (p.Glu87Lys) variant is a missense variant that has been reported in one study, in which it is found in a compound heterozygous state with a splice acceptor variant in a total of seven individuals from two Guamanian families. All seven individuals were diagnosed with Smith-McCort Dysplasia (Cohn et al. 2003). The unaffected mothers shared a common haplotype including the p.Glu87Lys variant, which is therefore likely to be an ancestral variant. The p.Glu87Lys variant is reported at a frequency of 0.000087 in the Latino population of the Exome Aggregation Consortium though this is based on one allele in a region of good sequence coverage so the variant is presumed to be rare. Functional studies by Dimitrov et al. (2009) in HeLa cells demonstrated that the p.Glu87Lys variant displays a pattern of cellular localization similar to wild type and does not affect the protein stability. The Glu87 residue is conserved. The evidence for this variant is limited. The p.Glu87Lys variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for Smith-McCort Dysplasia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Labcorp Genetics |
RCV002512700 | SCV003442641 | pathogenic | not provided | 2022-09-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 3189). This missense change has been observed in individual(s) with Smith-McCort dysplasia (PMID: 12491225). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs120074164, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 87 of the DYM protein (p.Glu87Lys). |
| OMIM | RCV000003340 | SCV000023498 | pathogenic | Smith-McCort dysplasia 1 | 2003-02-01 | no assertion criteria provided | literature only |