rs199422180
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_018136.5(ASPM):c.8508_8509del(p.Lys2837MetfsTer34) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
ASPM
NM_018136.5 frameshift
NM_018136.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.220
Genes affected
ASPM (HGNC:19048): (assembly factor for spindle microtubules) This gene is the human ortholog of the Drosophila melanogaster 'abnormal spindle' gene (asp), which is essential for normal mitotic spindle function in embryonic neuroblasts. Studies in mouse also suggest a role of this gene in mitotic spindle regulation, with a preferential role in regulating neurogenesis. Mutations in this gene are associated with microcephaly primary type 5. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASPM | NM_018136.5 | c.8508_8509del | p.Lys2837MetfsTer34 | frameshift_variant | 18/28 | ENST00000367409.9 | |
ASPM | NM_001206846.2 | c.4066-4579_4066-4578del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASPM | ENST00000367409.9 | c.8508_8509del | p.Lys2837MetfsTer34 | frameshift_variant | 18/28 | 1 | NM_018136.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249528Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134826
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460610Hom.: 0 AF XY: 0.00000688 AC XY: 5AN XY: 726638
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GnomAD4 genome ? Cov.: 32
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?
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Bravo
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ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
Microcephaly 5, primary, autosomal recessive Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at