Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2_SupportingPM4PP5_Moderate
The NM_018136.5(ASPM):c.10337del(p.Lys3446SerfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. Variant has been reported in ClinVar as Likely pathogenic (★).
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Verdict is Uncertain_significance. Variant got 5 ACMG points.
GnomAD3 genomesCov.: 31 GnomAD4 exome AF: 0.00000346AC: 5AN: 1446656Hom.: 0 AF XY: 0.00000278AC XY: 2AN XY: 720422
Submissions by phenotype
|Likely pathogenic, criteria provided, single submitter
|Oct 04, 2017
|The c.10337delA variant in the ASPM gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. It is not observed in large population cohorts (Lek et al., 2016). The c.10337delA variant causes a frameshift starting with codon Lysine 3446, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Lys3446SerfsX6. This variant is predicted to cause loss of normal protein function through protein truncation as 32 amino acids of the protein are replaced with 5 incorrect amino acids. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot becompletely excluded. -
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