ClinVar Miner

Submissions for variant NM_018136.5(ASPM):c.9730C>T (p.Arg3244Ter)

gnomAD frequency: 0.00001  dbSNP: rs199422195
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000020825 SCV000192296 pathogenic Microcephaly 5, primary, autosomal recessive 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000256150 SCV000322211 pathogenic not provided 2016-08-08 criteria provided, single submitter clinical testing The R3244X nonsense variant in the ASPM gene has been reported previously as a homozygous variant in multiple affected individuals in a family with MCPH (Gul et al., 2007). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
3billion RCV000020825 SCV002058419 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). 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 at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000021635, PMID:17849285). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Genome-Nilou Lab RCV000020825 SCV004177538 pathogenic Microcephaly 5, primary, autosomal recessive 2023-04-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000256150 SCV004293872 pathogenic not provided 2022-10-09 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: 21635). This premature translational stop signal has been observed in individual(s) with primary microcephaly (PMID: 17849285). This variant is present in population databases (rs199422195, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg3244*) 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).
GeneReviews RCV000020825 SCV000041412 not provided Microcephaly 5, primary, autosomal recessive no assertion provided literature only

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