chr9-120419924-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_018249.6(CDK5RAP2):c.4041G>A(p.Leu1347=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 1,613,676 control chromosomes in the GnomAD database, including 2,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.085 ( 1149 hom., cov: 33)
Exomes 𝑓: 0.033 ( 1569 hom. )
Consequence
CDK5RAP2
NM_018249.6 synonymous
NM_018249.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.26
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 9-120419924-C-T is Benign according to our data. Variant chr9-120419924-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 136706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-120419924-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.26 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDK5RAP2 | NM_018249.6 | c.4041G>A | p.Leu1347= | synonymous_variant | 27/38 | ENST00000349780.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDK5RAP2 | ENST00000349780.9 | c.4041G>A | p.Leu1347= | synonymous_variant | 27/38 | 1 | NM_018249.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0849 AC: 12903AN: 152064Hom.: 1141 Cov.: 33
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GnomAD3 exomes AF: 0.0400 AC: 10058AN: 251472Hom.: 561 AF XY: 0.0349 AC XY: 4740AN XY: 135914
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GnomAD4 exome AF: 0.0331 AC: 48307AN: 1461494Hom.: 1569 Cov.: 31 AF XY: 0.0315 AC XY: 22884AN XY: 727062
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GnomAD4 genome AF: 0.0851 AC: 12949AN: 152182Hom.: 1149 Cov.: 33 AF XY: 0.0840 AC XY: 6248AN XY: 74398
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
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, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
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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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at