ClinVar Miner

Submissions for variant NM_018136.5(ASPM):c.6919C>T (p.Gln2307Ter)

dbSNP: rs142865061
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina 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, Hôpital Robert Debré RCV000778956 SCV001432383 pathogenic Microcephaly 5, primary, autosomal recessive no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.