Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000605641 | SCV000731358 | likely pathogenic | Autosomal recessive primary microcephaly | 2016-12-22 | criteria provided, single submitter | clinical testing | The p.Gln1574X (NM_018136.4 c.4720C>T) variant in ASPM has not been reported in the literature. This nonsense variant leads to a premature termination codon at position 1574, which is predicted to lead to a truncated or absent protein. Bial lelic loss of function of the ASPM gene has been associated with primary microce phaly type 5. This variant has been identified in 1/6550 of Finnish chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs776034810). Although this variant has been seen in the general population, it s frequency is low enough to be consistent with a recessive carrier frequency. In summary, although additional studies are required to fully establish a null e ffect on the protein, the p.Gln1574X variant in ASPM is likely pathogenic for pr imary microcephaly type 5 in an autosomal recessive manner based upon its predic ted functional impact. |