Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000579333 | SCV000681302 | pathogenic | not provided | 2018-01-12 | criteria provided, single submitter | clinical testing | The Q3321X nonsense variant in the ASPM gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q3321X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). Additionally, other nonsense variants have been reported in the Human Gene Mutation Database in association with primary microcephaly (Stenson et al., 2014). |
Ambry Genetics | RCV002526938 | SCV003533975 | pathogenic | Inborn genetic diseases | 2021-09-24 | criteria provided, single submitter | clinical testing | The c.9961C>T (p.Q3321*) alteration, located in exon 25 (coding exon 25) of the ASPM gene, consists of a C to T substitution at nucleotide position 9961. This changes the amino acid from a glutamine (Q) to a stop codon at amino acid position 3321. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of <0.01% (1/250456) total alleles studied. The highest observed frequency was <0.01% (1/113030) of European (non-Finnish) alleles. This variant has been observed in three individuals from the same family, all of whom were included in a primary microcephaly cohort (Rasool, 2020). Based on the available evidence, this alteration is classified as pathogenic. |
Genome- |
RCV003451296 | SCV004177533 | pathogenic | Microcephaly 5, primary, autosomal recessive | 2023-04-11 | criteria provided, single submitter | clinical testing |