Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000145398 | SCV000192486 | pathogenic | Syndromic X-linked intellectual disability Najm type | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Broad Center for Mendelian Genomics, |
RCV000145398 | SCV001164453 | likely pathogenic | Syndromic X-linked intellectual disability Najm type | 2018-12-03 | criteria provided, single submitter | research | The heterozygous p.Gln692Ter variant in CASK was identified by our study in one individual with mental retardation and microcephaly with pontine and cerebellar hypoplasia. This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 692, which is predicted to lead to a truncated or absent protein. Loss of function of the CASK gene is an established disease mechanism in autosomal recessive mental retardation and microcephaly with pontine and cerebellar hypoplasia. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PVS1 (Richards 2015). |