rs75029577
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_018249.6(CDK5RAP2):c.1093-14G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 1,608,532 control chromosomes in the GnomAD database, including 733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.021 ( 57 hom., cov: 29)
Exomes 𝑓: 0.028 ( 676 hom. )
Consequence
CDK5RAP2
NM_018249.6 splice_polypyrimidine_tract, intron
NM_018249.6 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0770
Genes affected
CDK5RAP2 (HGNC:18672): (CDK5 regulatory subunit associated protein 2) This gene encodes a regulator of CDK5 (cyclin-dependent kinase 5) activity. The protein encoded by this gene is localized to the centrosome and Golgi complex, interacts with CDK5R1 and pericentrin (PCNT), plays a role in centriole engagement and microtubule nucleation, and has been linked to primary microcephaly and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 9-120518659-C-T is Benign according to our data. Variant chr9-120518659-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 136708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-120518659-C-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0214 (3245/151878) while in subpopulation NFE AF= 0.0291 (1975/67946). AF 95% confidence interval is 0.028. There are 57 homozygotes in gnomad4. There are 1686 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 57 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDK5RAP2 | NM_018249.6 | c.1093-14G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000349780.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDK5RAP2 | ENST00000349780.9 | c.1093-14G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_018249.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0214 AC: 3243AN: 151760Hom.: 57 Cov.: 29
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GnomAD3 exomes AF: 0.0238 AC: 5972AN: 251054Hom.: 86 AF XY: 0.0246 AC XY: 3342AN XY: 135682
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GnomAD4 exome AF: 0.0284 AC: 41338AN: 1456654Hom.: 676 Cov.: 29 AF XY: 0.0286 AC XY: 20733AN XY: 725094
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GnomAD4 genome ? AF: 0.0214 AC: 3245AN: 151878Hom.: 57 Cov.: 29 AF XY: 0.0227 AC XY: 1686AN XY: 74230
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 18, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Primary Microcephaly, Recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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