9-120463648-T-C

Variant summary

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

The NM_018249.6(CDK5RAP2):c.2107-2981A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,094 control chromosomes in the GnomAD database, including 8,485 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 0.33 (8485 hom., cov: 32)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK5RAP2	NM_018249.6	c.2107-2981A>G		intron_variant		ENST00000349780.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.2107-2981A>G		intron_variant		1	NM_018249.6	P4

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49654 AN: 151976 Hom.: 8477 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.327 AC: 49697 AN: 152094 Hom.: 8485 Cov.: 32 AF XY: 0.321 AC XY: 23852 AN XY: 74358

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.340

Alfa AF: 0.345 Hom.: 12940

Bravo AF: 0.324

Asia WGS AF: 0.194 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.66
Dann	Benign	0.29

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: rs7869290; hg19: chr9-123225926; COSMIC: COSV62573097;