Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
UNC Molecular Genetics Laboratory, |
RCV001095704 | SCV001251522 | likely pathogenic | Microcephaly 1, primary, autosomal recessive | criteria provided, single submitter | research | The MCPH1 c.2214+2T>C (p.?) variant is predicted to disrupt a splice site. | |
Gene |
RCV001567554 | SCV001791263 | likely pathogenic | not provided | 2021-01-15 | criteria provided, single submitter | clinical testing | Canonical splice site variant expected to result in aberrant splicing, though splice outcome is unknown; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV001567554 | SCV002285044 | uncertain significance | not provided | 2022-10-07 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 12 of the MCPH1 gene. However, it is currently unclear if variants that occur in this region of the gene cause disease. This variant is present in population databases (rs575037500, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MCPH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 873472). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |