9-120407932-G-C

Position:

• chr9-120407932-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+415C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 289,208 control chromosomes in the GnomAD database, including 92,259 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 0.80 (49095 hom., cov: 32)
  • Exomes 𝑓: 0.79 (43164 hom.)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.981

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	Protein	UniProt
CDK5RAP2	NM_018249.6	c.4726+415C>G		intron_variant		ENST00000349780.9	NP_060719.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.4726+415C>G		intron_variant		1	NM_018249.6	ENSP00000343818	P4

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121972 AN: 152082 Hom.: 49066 Cov.: 32

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.799

GnomAD4 exome AF: 0.792 AC: 108480 AN: 137008 Hom.: 43164 Cov.: 0 AF XY: 0.795 AC XY: 57877 AN XY: 72758

Gnomad4 AFR exome AF: 0.801

Gnomad4 AMR exome AF: 0.877

Gnomad4 ASJ exome AF: 0.742

Gnomad4 EAS exome AF: 0.870

Gnomad4 SAS exome AF: 0.820

Gnomad4 FIN exome AF: 0.836

Gnomad4 NFE exome AF: 0.767

Gnomad4 OTH exome AF: 0.792

GnomAD4 genome AF: 0.802 AC: 122057 AN: 152200 Hom.: 49095 Cov.: 32 AF XY: 0.806 AC XY: 59999 AN XY: 74410

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.847

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.875

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.799

Alfa AF: 0.700 Hom.: 2014

Bravo AF: 0.805

Asia WGS AF: 0.867 AC: 3015 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	0.052
DANN	Benign	0.45

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: rs914593; hg19: chr9-123170210;