Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetic Services Laboratory, |
RCV000193152 | SCV000246966 | pathogenic | Seckel syndrome 4 | 2013-02-08 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV000825515 | SCV000966826 | likely pathogenic | Autosomal recessive primary microcephaly | 2018-12-27 | criteria provided, single submitter | clinical testing | The p.Glu300ThrfsX7 variant in CENPJ has been reported in one individual with Se ckel syndrome (ClinVar Variation ID #210670). It has been identified in 2/113580 of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Although this variant has been seen in the general population, its frequency is low enoug h to be consistent with a recessive carrier frequency. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 300 and leads to a premature termination codon 7 amino acids downst ream. This alteration is then predicted to lead to a truncated or absent protein . Biallelic loss of function of the CENPJ gene has been strongly associated with autosomal recessive primary microcephaly with or without clinical features of S eckel syndrome. In summary, although additional studies are required to fully es tablish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive primary microcephaly with or withou t clinical features of Seckel syndrome. ACMG/AMP Criteria applied: PM2, PVS1. |