Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetic Services Laboratory, |
RCV000145556 | SCV000192649 | pathogenic | Microcephaly 6, primary, autosomal recessive | 2013-02-08 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000762912 | SCV000893324 | likely pathogenic | Microcephaly 6, primary, autosomal recessive; Seckel syndrome 4 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| DASA | RCV000145556 | SCV002588764 | pathogenic | Microcephaly 6, primary, autosomal recessive | 2022-11-03 | criteria provided, single submitter | clinical testing | The c.1586C>G;p.(Ser529*) variant creates a premature translational stop signal in the CENPJ gene. It is expected to result in an absent or disrupted protein product - PVS1. ClinVar contains an entry for this variant (Clinvar ID: 158194) - PS4_supporting. The variant is present at low allele frequencies population databases (rs202058504 – gnomAD 0.001169%; ABraOM no frequency - https://abraom.ib.usp.br/) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic. |
| Gene |
RCV002466446 | SCV002762195 | uncertain significance | not provided | 2022-06-08 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31589614) |
| Invitae | RCV002466446 | SCV003488973 | pathogenic | not provided | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser529*) in the CENPJ gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CENPJ are known to be pathogenic (PMID: 15793586, 16900296, 20522431). This variant is present in population databases (rs202058504, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CENPJ-related conditions. ClinVar contains an entry for this variant (Variation ID: 158194). For these reasons, this variant has been classified as Pathogenic. |
| Molecular Genetics Department, |
RCV000145556 | SCV004801811 | likely pathogenic | Microcephaly 6, primary, autosomal recessive | criteria provided, single submitter | clinical testing | A previously undescribed nucleotide variant creates a premature translation stop signal p.Ser529Ter in the CENPJ gene. The variant was observed in presumably compound heterozygous state with another LoF variant (phase not tested) in an individual affected with microcephaly and micrognathia. Homozygous and compound heterozygous variants are reported in patients with Microcephaly 6, primary, autosomal recessive, 608393, and Seckel syndrome 4, 613676. The variant is present in gnomAD population database at low frequency (24/250986 chromosomes, no homozygotes). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as likely pathogenic. | |
| Service de Génétique Moléculaire, |
RCV000145556 | SCV001432342 | pathogenic | Microcephaly 6, primary, autosomal recessive | no assertion criteria provided | clinical testing |