rs16909739

chr9-120403829-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018249.6(CDK5RAP2):c.5041+207T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 152,292 control chromosomes in the GnomAD database, including 323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.056 (323 hom., cov: 32)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.21

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-120403829-A-G is Benign according to our data. Variant chr9-120403829-A-G is described in ClinVar as [Benign]. Clinvar id is 1293096.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK5RAP2	NM_018249.6	c.5041+207T>C		intron_variant		ENST00000349780.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.5041+207T>C		intron_variant		1	NM_018249.6	P4

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8520 AN: 152174 Hom.: 324 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0946

Gnomad FIN AF: 0.0536

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0822

Gnomad OTH AF: 0.0606

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

GnomAD4 genome AF: 0.0559 AC: 8515 AN: 152292 Hom.: 323 Cov.: 32 AF XY: 0.0561 AC XY: 4179 AN XY: 74480

Gnomad4 AFR AF: 0.0149

Gnomad4 AMR AF: 0.0535

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0949

Gnomad4 FIN AF: 0.0536

Gnomad4 NFE AF: 0.0822

Gnomad4 OTH AF: 0.0600

Alfa AF: 0.0629 Hom.: 55

Bravo AF: 0.0515

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.022
Dann	Benign	0.52

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: rs16909739; hg19: chr9-123166107;