Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000005248 | SCV000192278 | pathogenic | Microcephaly 5, primary, autosomal recessive | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000214564 | SCV000278803 | pathogenic | not provided | 2022-03-21 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 23611254, 15355437, 30086807, 19028728) |
Athena Diagnostics Inc | RCV000214564 | SCV000840899 | pathogenic | not provided | 2018-05-14 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193347 | SCV001362104 | pathogenic | Autosomal recessive primary microcephaly | 2019-08-07 | criteria provided, single submitter | clinical testing | Variant summary: ASPM c.9178C>T (p.Gln3060X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.6e-05 in 249856 control chromosomes (gnomAD). c.9178C>T has been reported in the literature in individuals affected with Primary autosomal recessive microcephaly (e.g. Kumar_2004). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Revvity Omics, |
RCV000005248 | SCV002019651 | pathogenic | Microcephaly 5, primary, autosomal recessive | 2020-10-20 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000214564 | SCV002230153 | pathogenic | not provided | 2023-12-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln3060*) in the ASPM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ASPM are known to be pathogenic (PMID: 19028728, 23611254). This variant is present in population databases (rs137852994, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with primary microcephaly (PMID: 15355437, 19028728, 23611254). ClinVar contains an entry for this variant (Variation ID: 4960). For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000005248 | SCV004177558 | pathogenic | Microcephaly 5, primary, autosomal recessive | 2023-04-11 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000005248 | SCV000025426 | pathogenic | Microcephaly 5, primary, autosomal recessive | 2004-10-01 | no assertion criteria provided | literature only | |
Gene |
RCV000005248 | SCV000041397 | not provided | Microcephaly 5, primary, autosomal recessive | no assertion provided | literature only |