ClinVar Miner

Submissions for variant NM_018136.5(ASPM):c.7125_7128dup (p.Gln2377fs)

dbSNP: rs587783263
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000145177 SCV000192226 pathogenic Microcephaly 5, primary, autosomal recessive 2013-12-05 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000790789 SCV000345866 pathogenic not provided 2016-09-20 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000790789 SCV001502569 pathogenic not provided 2020-12-01 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000145177 SCV002019899 pathogenic Microcephaly 5, primary, autosomal recessive 2021-01-29 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000145177 SCV002787127 likely pathogenic Microcephaly 5, primary, autosomal recessive 2021-10-12 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000145177 SCV004178589 likely pathogenic Microcephaly 5, primary, autosomal recessive 2023-04-11 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV000145177 SCV004239052 pathogenic Microcephaly 5, primary, autosomal recessive 2023-11-15 criteria provided, single submitter clinical testing This ASPM variant (rs587783263 ) is rare (<0.1%) in a large population dataset (gnomAD v4.0.0: 4/1461022 total alleles; 0.0003%; no homozygotes). It has been reported in ClinVar (Variation ID 157864), but has not been reported in the literature in individuals known to be affected with microcephaly and having biallelic ASPM variants, to our knowledge. This frameshift variant results in a premature stop codon in exon 18 of 28, likely leading to nonsense-mediated decay and lack of protein production. We consider c.7125_7128dup in ASPM to be pathogenic.
GeneDx RCV000790789 SCV005443035 pathogenic not provided 2024-07-02 criteria provided, single submitter clinical testing Frameshift 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: 31980526, 31069529)
Labcorp Genetics (formerly Invitae), Labcorp RCV000790789 SCV005722351 pathogenic not provided 2024-11-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln2377Thrfs*26) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with microcephaly (PMID: 31069529). ClinVar contains an entry for this variant (Variation ID: 157864). For these reasons, this variant has been classified as Pathogenic.

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.