9-120404641-C-T

Position:

• chr9-120404641-C-T

Variant summary

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

The NM_018249.6(CDK5RAP2):​c.4964-528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,010 control chromosomes in the GnomAD database, including 2,560 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 0.18 (2560 hom., cov: 32)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK5RAP2	NM_018249.6	c.4964-528G>A		intron_variant		ENST00000349780.9	NP_060719.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.4964-528G>A		intron_variant		1	NM_018249.6	ENSP00000343818	P4

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27203 AN: 151892 Hom.: 2561 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.182

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.179 AC: 27221 AN: 152010 Hom.: 2560 Cov.: 32 AF XY: 0.179 AC XY: 13307 AN XY: 74296

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.180

Alfa AF: 0.165 Hom.: 1062

Bravo AF: 0.183

Asia WGS AF: 0.222 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.6
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3780674; hg19: chr9-123166919; COSMIC: COSV62573066; COSMIC: COSV62573066;