rs2282168

Positions:

• chr9-120407440-C-G
• chr9-120407440-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_018249.6(CDK5RAP2):​c.4727-192G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 620,264 control chromosomes in the GnomAD database, including 201,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (49705 hom., cov: 32)
  • Exomes 𝑓: 0.80 (151314 hom.)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.806

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 9-120407440-C-G is Benign according to our data. Variant chr9-120407440-C-G is described in ClinVar as [Benign]. Clinvar id is 678319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK5RAP2	NM_018249.6	c.4727-192G>C		intron_variant		ENST00000349780.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.4727-192G>C		intron_variant		1	NM_018249.6	P4

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122707 AN: 152054 Hom.: 49664 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.805

GnomAD4 exome AF: 0.803 AC: 375856 AN: 468092 Hom.: 151314 Cov.: 4 AF XY: 0.804 AC XY: 199266 AN XY: 247828

Gnomad4 AFR exome AF: 0.821

Gnomad4 AMR exome AF: 0.891

Gnomad4 ASJ exome AF: 0.761

Gnomad4 EAS exome AF: 0.883

Gnomad4 SAS exome AF: 0.832

Gnomad4 FIN exome AF: 0.844

Gnomad4 NFE exome AF: 0.778

Gnomad4 OTH exome AF: 0.804

GnomAD4 genome AF: 0.807 AC: 122806 AN: 152172 Hom.: 49705 Cov.: 32 AF XY: 0.811 AC XY: 60381 AN XY: 74412

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.876

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.807

Alfa AF: 0.704 Hom.: 2018

Bravo AF: 0.811

Asia WGS AF: 0.888 AC: 3087 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.33
CADD	Benign	19
DANN	Benign	0.64

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: rs2282168; hg19: chr9-123169718;