9-120407793-G-A

Position:

• chr9-120407793-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018249.6(CDK5RAP2):​c.4727-545C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 180,586 control chromosomes in the GnomAD database, including 45,240 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 0.69 (37066 hom., cov: 29)
  • Exomes 𝑓: 0.74 (8174 hom.)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.959

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK5RAP2	NM_018249.6	c.4727-545C>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.4727-545C>T		intron_variant		1	NM_018249.6	ENSP00000343818	P4

Frequencies

GnomAD3 genomes AF: 0.686 AC: 103983 AN: 151532 Hom.: 37068 Cov.: 29

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.713

GnomAD4 exome AF: 0.741 AC: 21446 AN: 28942 Hom.: 8174 Cov.: 0 AF XY: 0.746 AC XY: 11263 AN XY: 15104

Gnomad4 AFR exome AF: 0.430

Gnomad4 AMR exome AF: 0.835

Gnomad4 ASJ exome AF: 0.664

Gnomad4 EAS exome AF: 0.804

Gnomad4 SAS exome AF: 0.796

Gnomad4 FIN exome AF: 0.765

Gnomad4 NFE exome AF: 0.716

Gnomad4 OTH exome AF: 0.721

GnomAD4 genome AF: 0.686 AC: 104022 AN: 151644 Hom.: 37066 Cov.: 29 AF XY: 0.693 AC XY: 51301 AN XY: 74080

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.832

Gnomad4 SAS AF: 0.816

Gnomad4 FIN AF: 0.819

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.710

Alfa AF: 0.691 Hom.: 5790

Bravo AF: 0.687

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.72

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: rs1888893; hg19: chr9-123170071;