rs267606718
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001194998.2(CEP152):c.2959C>T(p.Arg987*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,576,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
CEP152
NM_001194998.2 stop_gained
NM_001194998.2 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 2.31
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 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CEP152 | NM_001194998.2 | c.2959C>T | p.Arg987* | stop_gained | 20/27 | ENST00000380950.7 | NP_001181927.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CEP152 | ENST00000380950.7 | c.2959C>T | p.Arg987* | stop_gained | 20/27 | 1 | NM_001194998.2 | ENSP00000370337.2 | ||
CEP152 | ENST00000399334.7 | c.2959C>T | p.Arg987* | stop_gained | 20/26 | 1 | ENSP00000382271.3 | |||
CEP152 | ENST00000325747.9 | c.2680C>T | p.Arg894* | stop_gained | 19/25 | 1 | ENSP00000321000.5 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151834Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000905 AC: 2AN: 220876Hom.: 0 AF XY: 0.00000835 AC XY: 1AN XY: 119752
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GnomAD4 exome AF: 0.0000105 AC: 15AN: 1424772Hom.: 0 Cov.: 32 AF XY: 0.00000567 AC XY: 4AN XY: 705272
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 151834Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74144
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Microcephaly 9, primary, autosomal recessive Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Universite Libre de Bruxelles | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 09, 2010 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 09, 2023 | This sequence change creates a premature translational stop signal (p.Arg987*) 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). This variant is present in population databases (rs267606718, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with CEP152-related conditions (PMID: 20598275). ClinVar contains an entry for this variant (Variation ID: 56). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | CEP152: PVS1, PM2 - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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