rs10818464

Variant names:

• chr9-120551719-C-A
• rs10818464
• NM_018249.6:c.196-817G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-120551719-C-A
• chr9-120551719-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018249.6(CDK5RAP2):​c.196-817G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,040 control chromosomes in the GnomAD database, including 33,469 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 0.66 (33469 hom., cov: 32)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.741
• Publications: 4 publications found

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]

CDK5RAP2 Gene-Disease associations (from GenCC):

• autosomal recessive primary microcephaly

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• microcephaly 3, primary, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• corpus callosum, agenesis of

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5RAP2	NM_018249.6	c.196-817G>T		intron_variant	Intron 3 of 37	ENST00000349780.9	NP_060719.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.196-817G>T		intron_variant	Intron 3 of 37	1	NM_018249.6	ENSP00000343818.4

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99607 AN: 151922 Hom.: 33456 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.655 AC: 99652 AN: 152040 Hom.: 33469 Cov.: 32 AF XY: 0.655 AC XY: 48726 AN XY: 74340

African (AFR) AF: 0.500 AC: 20690 AN: 41418

American (AMR) AF: 0.652 AC: 9963 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2585 AN: 3470

East Asian (EAS) AF: 0.622 AC: 3219 AN: 5176

South Asian (SAS) AF: 0.691 AC: 3329 AN: 4820

European-Finnish (FIN) AF: 0.761 AC: 8060 AN: 10592

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49721 AN: 67976

Other (OTH) AF: 0.660 AC: 1393 AN: 2112

Alfa AF: 0.695 Hom.: 53926

Bravo AF: 0.640

Asia WGS AF: 0.614 AC: 2133 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.43
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10818464; hg19: chr9-123313997;