Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000778956 | SCV000915383 | uncertain significance | Microcephaly 5, primary, autosomal recessive | 2019-01-11 | criteria provided, single submitter | clinical testing | The ASPM c.6919C>T (p.Gln2307Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The p.Gln2307Ter variant has been reported in one study in which it is found in a compound heterozygous state with a null variant in two siblings with autosomal recessive primary microcephaly (Letard et al. 2018). Control data are unavailable for this variant, which is reported at a frequency of 0.00006541 in the African population of the Genome Aggregation Database but this is based on one allele in a region of good sequence coverage so the variant is presumed to be rare. Based on the limited clinical information and potential impact of stop-gained variants, the p.Gln2307Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive primary microcephaly. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV001873177 | SCV002219315 | pathogenic | not provided | 2022-09-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 632095). This premature translational stop signal has been observed in individual(s) with autosomal recessive primary microcephaly (PMID: 29243349). This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Gln2307*) 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). |
Service de Génétique Moléculaire, |
RCV000778956 | SCV001432383 | pathogenic | Microcephaly 5, primary, autosomal recessive | no assertion criteria provided | clinical testing |