Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV004018309 | SCV004847478 | likely pathogenic | Microcephaly 2, primary, autosomal recessive, with or without cortical malformations | 2024-03-28 | criteria provided, single submitter | clinical testing | The p.Gln499X variant in WDR62 has not been previously reported in individuals with microcephaly but has been identified in 0.00007% (1/1459130) of pan ethnic chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.4.0.0). This nonsense variant leads to a premature termination codon at position 499, which is predicted to lead to a truncated or absent protein. Biallelic loss of function of the WDR62 gene is an established disease mechanism in autosomal recessive microcephaly (with or without cortical malformations). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive primary microcephaly. ACMG/AMP Criteria applied: PVS1, PM2_Supporting. |