rs914592

Positions:

• chr9-120407889-G-A
• chr9-120407889-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018249.6(CDK5RAP2):​c.4726+458C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 254,970 control chromosomes in the GnomAD database, including 82,515 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (50031 hom., cov: 31)
  • Exomes 𝑓: 0.79 (32484 hom.)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK5RAP2	NM_018249.6	c.4726+458C>T		intron_variant		ENST00000349780.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.4726+458C>T		intron_variant		1	NM_018249.6	P4

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123078 AN: 152020 Hom.: 49991 Cov.: 31

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.806

GnomAD4 exome AF: 0.792 AC: 81404 AN: 102832 Hom.: 32484 Cov.: 0 AF XY: 0.793 AC XY: 42798 AN XY: 53974

Gnomad4 AFR exome AF: 0.828

Gnomad4 AMR exome AF: 0.879

Gnomad4 ASJ exome AF: 0.742

Gnomad4 EAS exome AF: 0.874

Gnomad4 SAS exome AF: 0.817

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.767

Gnomad4 OTH exome AF: 0.796

GnomAD4 genome AF: 0.810 AC: 123176 AN: 152138 Hom.: 50031 Cov.: 31 AF XY: 0.814 AC XY: 60515 AN XY: 74360

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.875

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.808

Alfa AF: 0.788 Hom.: 68875

Bravo AF: 0.814

Asia WGS AF: 0.886 AC: 3082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs914592; hg19: chr9-123170167;