rs770422442
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001194998.2(CEP152):c.540+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Consequence
CEP152
NM_001194998.2 splice_donor_region, intron
NM_001194998.2 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0005958
2
Clinical Significance
Conservation
PhyloP100: -0.227
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP152 | NM_001194998.2 | c.540+6G>A | splice_donor_region_variant, intron_variant | ENST00000380950.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP152 | ENST00000380950.7 | c.540+6G>A | splice_donor_region_variant, intron_variant | 1 | NM_001194998.2 | A2 | |||
CEP152 | ENST00000325747.9 | c.261+366G>A | intron_variant | 1 | A2 | ||||
CEP152 | ENST00000399334.7 | c.540+6G>A | splice_donor_region_variant, intron_variant | 1 | P2 | ||||
CEP152 | ENST00000560322.5 | c.540+6G>A | splice_donor_region_variant, intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247776Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134616
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GnomAD4 exome Cov.: 32
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74370
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 31, 2016 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 23, 2021 | The c.540+6G>A intronic alteration consists of a G to A substitution nucleotides after coding exon 4 in the CEP152 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at