ClinVar Miner

Submissions for variant NM_018136.5(ASPM):c.7782_7783del (p.Lys2595fs) (rs199422173)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000020796 SCV000192246 pathogenic Primary autosomal recessive microcephaly 5 2013-12-20 criteria provided, single submitter clinical testing
GeneDx RCV000365777 SCV000329089 pathogenic not provided 2018-04-17 criteria provided, single submitter clinical testing The c.7782_7783delGA pathogenic variant in the ASPM gene has been reported multiple times previously in association with autosomal recessive primary microcephaly (MCPH) (Nicholas et al., 2009; Passemard et al., 2009; Tan et al., 2014). The c.7782_7783delGA pathogenic variant causes a frameshift starting with codon Lysine 2595, changes this amino acid to a Serine residue and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Lys2595SerfsX6. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.7782_7783delGA variant is observed in 16/34096 (0.05%) alleles from individuals of Latino background (Lek et al., 2016).
Invitae RCV000365777 SCV000938337 pathogenic not provided 2018-12-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys2595Serfs*6) in the ASPM gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs199422173, ExAC 0.07%). This variant has been observed in several individuals affected with autosomal recessive primary microcephaly (MCPH) (PMID: 19028728, 23611254, 29644084). ClinVar contains an entry for this variant (Variation ID: 21606). Loss-of-function variants in ASPM are known to be pathogenic (PMID: 19028728, 23611254). For these reasons, this variant has been classified as Pathogenic.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000020796 SCV000999002 pathogenic Primary autosomal recessive microcephaly 5 2019-09-02 criteria provided, single submitter clinical testing A Homozygous two base pair deletion in exon 18 of the ASPM gene that results in a frameshift and premature truncation of the protein 6 amino acids downstream to codon 2595 was detected. The observed variant c.7782_7783del (p.Lys2595SerfsTer6) has not been reported in the 1000 genomes database and has a minor allele frequency of 0.03% in the ExAC database. The in silico prediction of the variant is damaging by MutationTaster2. The reference region is conserved across mammals.
Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn RCV000856804 SCV000999370 pathogenic Primary autosomal recessive microcephaly 1 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000365777 SCV001246852 pathogenic not provided 2019-03-01 criteria provided, single submitter clinical testing
GeneReviews RCV000020796 SCV000041381 pathologic Primary autosomal recessive microcephaly 5 2009-09-01 no assertion criteria provided curation Converted during submission to Pathogenic.

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