Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000145078 | SCV000192119 | pathogenic | Microcephaly 5, primary, autosomal recessive | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Department Of Translational Genomics |
RCV000171162 | SCV000221358 | likely pathogenic | not provided | criteria provided, single submitter | research | ||
Baylor Genetics | RCV000145078 | SCV001522639 | pathogenic | Microcephaly 5, primary, autosomal recessive | 2019-10-30 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
Revvity Omics, |
RCV000145078 | SCV002019640 | pathogenic | Microcephaly 5, primary, autosomal recessive | 2022-06-28 | criteria provided, single submitter | clinical testing | |
Broad Institute Rare Disease Group, |
RCV000145078 | SCV002507044 | pathogenic | Microcephaly 5, primary, autosomal recessive | 2022-05-04 | criteria provided, single submitter | curation | The homozygous p.Gln380Ter variant in ASPM was identified by our study in 2 siblings with autosomal recessive primary microcephaly 5. The variant has been reported in 1 Middle Eastern individual with autosomal recessive primary microcephaly 5 (PMID: 23611254), but was absent from large population studies. This variant has also been reported in ClinVar (Variation ID: 157777) as pathogenic by Genetic Services Laboratory, University of Chicago and Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City, and as likely pathogenic by Developmental Genetics Unit, King Faisal Specialist Hospital & Research Centre. This nonsense variant leads to a premature termination codon at position 380, which is predicted to lead to a truncated or absent protein. Loss of function of the ASPM gene is an established disease mechanism in autosomal recessive primary microcephaly 5. The presence of this variant in at least 2 homozygotes, and in 2 individuals with autosomal recessive primary microcephaly 5 increases the likelihood that the p.Gln380Ter variant is pathogenic (PMID: 23611254). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive primary microcephaly 5 based on the predicted impact of the variant, its absence from control populations, and its homozygous appearance in 3 affected individuals. ACMG/AMP Criteria applied: PVS1, PM2, PM3 (Richards 2015). |
Genome- |
RCV000145078 | SCV004178771 | pathogenic | Microcephaly 5, primary, autosomal recessive | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Biochemical Molecular Genetic Laboratory, |
RCV000145078 | SCV001132965 | pathogenic | Microcephaly 5, primary, autosomal recessive | 2019-08-25 | no assertion criteria provided | clinical testing |