9-120389963-A-C

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.5579-176T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 660,442 control chromosomes in the GnomAD database, including 160,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (36230 hom., cov: 33)
  • Exomes 𝑓: 0.70 (124003 hom.)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.47

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=-1.0).
• BP6: Variant 9-120389963-A-C is Benign according to our data. Variant chr9-120389963-A-C is described in ClinVar as [Benign]. Clinvar id is 678322.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK5RAP2	NM_018249.6	c.5579-176T>G		intron_variant		ENST00000349780.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.5579-176T>G		intron_variant		1	NM_018249.6	P4

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104711 AN: 152028 Hom.: 36208 Cov.: 33

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.691

GnomAD4 exome AF: 0.696 AC: 353813 AN: 508298 Hom.: 124003 Cov.: 4 AF XY: 0.693 AC XY: 187826 AN XY: 270842

Gnomad4 AFR exome AF: 0.655

Gnomad4 AMR exome AF: 0.783

Gnomad4 ASJ exome AF: 0.647

Gnomad4 EAS exome AF: 0.789

Gnomad4 SAS exome AF: 0.664

Gnomad4 FIN exome AF: 0.763

Gnomad4 NFE exome AF: 0.680

Gnomad4 OTH exome AF: 0.690

GnomAD4 genome AF: 0.689 AC: 104786 AN: 152144 Hom.: 36230 Cov.: 33 AF XY: 0.693 AC XY: 51551 AN XY: 74358

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.691

Alfa AF: 0.683 Hom.: 9898

Bravo AF: 0.689

Asia WGS AF: 0.761 AC: 2646 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

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.021
Dann	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs2297456; hg19: chr9-123152241;