9-120389982-G-A

Position:

• chr9-120389982-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018249.6(CDK5RAP2):​c.5579-195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 621,432 control chromosomes in the GnomAD database, including 2,005 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (391 hom., cov: 33)
  • Exomes 𝑓: 0.049 (1614 hom.)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.924

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-120389982-G-A is Benign according to our data. Variant chr9-120389982-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1214563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK5RAP2	NM_018249.6	c.5579-195C>T		intron_variant		ENST00000349780.9	NP_060719.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.5579-195C>T		intron_variant		1	NM_018249.6	ENSP00000343818	P4

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 7046 AN: 152160 Hom.: 392 Cov.: 33

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.0871

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0425

GnomAD4 exome AF: 0.0490 AC: 22994 AN: 469154 Hom.: 1614 Cov.: 2 AF XY: 0.0496 AC XY: 12344 AN XY: 249062

Gnomad4 AFR exome AF: 0.0461

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.0210

Gnomad4 EAS exome AF: 0.268

Gnomad4 SAS exome AF: 0.0740

Gnomad4 FIN exome AF: 0.0479

Gnomad4 NFE exome AF: 0.0170

Gnomad4 OTH exome AF: 0.0472

GnomAD4 genome AF: 0.0463 AC: 7047 AN: 152278 Hom.: 391 Cov.: 33 AF XY: 0.0498 AC XY: 3710 AN XY: 74452

Gnomad4 AFR AF: 0.0496

Gnomad4 AMR AF: 0.0855

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.0872

Gnomad4 FIN AF: 0.0524

Gnomad4 NFE AF: 0.0167

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.00936 Hom.: 1

Bravo AF: 0.0482

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.51
DANN	Benign	0.48
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: rs2297455; hg19: chr9-123152260;