Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
3billion | RCV000005249 | SCV002058172 | pathogenic | Microcephaly 5, primary, autosomal recessive | 2022-01-03 | criteria provided, single submitter | clinical testing | Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS).The variant has been reported to be associated with ASPM related disorder (ClinVar ID: VCV000004961, PMID:15355437).It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000004, PM2_M). The variant has been reported to be in trans as homozygous in at least one similarly affected unrelated individual (PMID: 15355437,PM3_P). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
Invitae | RCV002512801 | SCV003524015 | pathogenic | not provided | 2022-05-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp1326*) 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 (rs137852995, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with primary microcephaly (PMID: 15355437, 31853109). ClinVar contains an entry for this variant (Variation ID: 4961). For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000005249 | SCV004178687 | pathogenic | Microcephaly 5, primary, autosomal recessive | 2023-04-11 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000005249 | SCV000025427 | pathogenic | Microcephaly 5, primary, autosomal recessive | 2004-10-01 | no assertion criteria provided | literature only | |
Gene |
RCV000005249 | SCV000041354 | not provided | Microcephaly 5, primary, autosomal recessive | no assertion provided | literature only |