rs10984956

chr9-120562567-T-C

Variant summary

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

The NM_018249.6(CDK5RAP2):c.195+5754A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,020 control chromosomes in the GnomAD database, including 1,242 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 0.11 (1242 hom., cov: 31)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK5RAP2	NM_018249.6	c.195+5754A>G		intron_variant		ENST00000349780.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.195+5754A>G		intron_variant		1	NM_018249.6	P4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16689 AN: 151902 Hom.: 1242 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0745

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0652

Gnomad OTH AF: 0.0920

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.110 AC: 16700 AN: 152020 Hom.: 1242 Cov.: 31 AF XY: 0.112 AC XY: 8288 AN XY: 74296

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0692

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0745

Gnomad4 NFE AF: 0.0652

Gnomad4 OTH AF: 0.0919

Alfa AF: 0.0744 Hom.: 710

Bravo AF: 0.115

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.56
Dann	Benign	0.67

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: rs10984956; hg19: chr9-123324845;