9-120407793-G-T

Position:

• chr9-120407793-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_018249.6(CDK5RAP2):​c.4727-545C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 180,746 control chromosomes in the GnomAD database, including 31 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 0.014 (31 hom., cov: 29)
  • Exomes 𝑓: 0.0042 (0 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=-0.83).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0142 (2161/151742) while in subpopulation AFR AF= 0.041 (1695/41320). AF 95% confidence interval is 0.0394. There are 31 homozygotes in gnomad4. There are 1011 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2159 AN: 151630 Hom.: 31 Cov.: 29

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00637

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00644

Gnomad FIN AF: 0.000286

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00288

Gnomad OTH AF: 0.0111

GnomAD4 exome AF: 0.00417 AC: 121 AN: 29004 Hom.: 0 Cov.: 0 AF XY: 0.00370 AC XY: 56 AN XY: 15130

Gnomad4 AFR exome AF: 0.0322

Gnomad4 AMR exome AF: 0.00573

Gnomad4 ASJ exome AF: 0.0261

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00568

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00255

Gnomad4 OTH exome AF: 0.00634

GnomAD4 genome AF: 0.0142 AC: 2161 AN: 151742 Hom.: 31 Cov.: 29 AF XY: 0.0136 AC XY: 1011 AN XY: 74122

Gnomad4 AFR AF: 0.0410

Gnomad4 AMR AF: 0.00636

Gnomad4 ASJ AF: 0.0303

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00624

Gnomad4 FIN AF: 0.000286

Gnomad4 NFE AF: 0.00288

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0000885 Hom.: 5790

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.9
DANN	Benign	0.71

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;