rs587783414
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Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001194998.2(CEP152):c.1155delC(p.Thr386fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
CEP152
NM_001194998.2 frameshift
NM_001194998.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -2.04
Genes affected
CEP152 (HGNC:29298): (centrosomal protein 152) This gene encodes a protein that is thought to be involved with centrosome function. Mutations in this gene have been associated with primary microcephaly (MCPH4). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 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;
PP5
Variant 15-48788818-TG-T is Pathogenic according to our data. Variant chr15-48788818-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 158223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CEP152 | NM_001194998.2 | c.1155delC | p.Thr386fs | frameshift_variant | 9/27 | ENST00000380950.7 | NP_001181927.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CEP152 | ENST00000380950.7 | c.1155delC | p.Thr386fs | frameshift_variant | 9/27 | 1 | NM_001194998.2 | ENSP00000370337.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000481 AC: 12AN: 249572Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135402
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GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727232
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Microcephaly 9, primary, autosomal recessive Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 24, 2013 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 15, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 158223). This variant has not been reported in the literature in individuals affected with CEP152-related conditions. This variant is present in population databases (rs587783414, gnomAD 0.04%). This sequence change creates a premature translational stop signal (p.Thr386Profs*13) in the CEP152 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP152 are known to be pathogenic (PMID: 21131973). - |
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