9-120569993-A-T

Position:

• chr9-120569993-A-T

Variant summary

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

The NM_018249.6(CDK5RAP2):​c.128-1605T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,082 control chromosomes in the GnomAD database, including 2,393 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 0.17 (2393 hom., cov: 32)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK5RAP2	NM_018249.6	c.128-1605T>A		intron_variant		ENST00000349780.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.128-1605T>A		intron_variant		1	NM_018249.6	P4

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26371 AN: 151964 Hom.: 2394 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.173 AC: 26369 AN: 152082 Hom.: 2393 Cov.: 32 AF XY: 0.173 AC XY: 12830 AN XY: 74332

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.0846

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.197

Alfa AF: 0.184 Hom.: 329

Bravo AF: 0.175

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.78

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: rs13299371; hg19: chr9-123332271; COSMIC: COSV62573120; COSMIC: COSV62573120;