rs2069454

chr7-151055895-C-G

Variant summary

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

The NM_004935.4(CDK5):c.313-47G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.046 in 1,325,908 control chromosomes in the GnomAD database, including 1,541 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 0.047 (227 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1314 hom.)
• Consequence: CDK5 NM_004935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

Genes affected

CDK5 (HGNC:1774): (cyclin dependent kinase 5) This gene encodes a proline-directed serine/threonine kinase that is a member of the cyclin-dependent kinase family of proteins. Unlike other members of the family, the protein encoded by this gene does not directly control cell cycle regulation. Instead the protein, which is predominantly expressed at high levels in mammalian postmitotic central nervous system neurons, functions in diverse processes such as synaptic plasticity and neuronal migration through phosphorylation of proteins required for cytoskeletal organization, endocytosis and exocytosis, and apoptosis. In humans, an allelic variant of the gene that results in undetectable levels of the protein has been associated with lethal autosomal recessive lissencephaly-7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK5	NM_004935.4	c.313-47G>C		intron_variant		ENST00000485972.6
CDK5	NM_001164410.3	c.313-289G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK5	ENST00000485972.6	c.313-47G>C		intron_variant		1	NM_004935.4	P1
CDK5	ENST00000297518.4	c.313-289G>C		intron_variant		1
CDK5	ENST00000476691.1	n.466G>C		non_coding_transcript_exon_variant	1/2	4
CDK5	ENST00000487703.5	n.677-47G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0474 AC: 7217 AN: 152184 Hom.: 229 Cov.: 32

Gnomad AFR AF: 0.0671

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.00981

Gnomad SAS AF: 0.0524

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0402

GnomAD3 exomes AF: 0.0406 AC: 7201 AN: 177296 Hom.: 180 AF XY: 0.0422 AC XY: 3985 AN XY: 94372

Gnomad AFR exome AF: 0.0685

Gnomad AMR exome AF: 0.0225

Gnomad ASJ exome AF: 0.0340

Gnomad EAS exome AF: 0.00953

Gnomad SAS exome AF: 0.0576

Gnomad FIN exome AF: 0.0266

Gnomad NFE exome AF: 0.0473

Gnomad OTH exome AF: 0.0392

GnomAD4 exome AF: 0.0458 AC: 53778 AN: 1173606 Hom.: 1314 Cov.: 16 AF XY: 0.0463 AC XY: 27334 AN XY: 590730

Gnomad4 AFR exome AF: 0.0694

Gnomad4 AMR exome AF: 0.0243

Gnomad4 ASJ exome AF: 0.0357

Gnomad4 EAS exome AF: 0.0104

Gnomad4 SAS exome AF: 0.0608

Gnomad4 FIN exome AF: 0.0303

Gnomad4 NFE exome AF: 0.0474

Gnomad4 OTH exome AF: 0.0441

GnomAD4 genome AF: 0.0474 AC: 7224 AN: 152302 Hom.: 227 Cov.: 32 AF XY: 0.0466 AC XY: 3469 AN XY: 74470

Gnomad4 AFR AF: 0.0672

Gnomad4 AMR AF: 0.0333

Gnomad4 ASJ AF: 0.0377

Gnomad4 EAS AF: 0.00983

Gnomad4 SAS AF: 0.0524

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0445

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0430 Hom.: 25

Bravo AF: 0.0478

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.5
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2069454; hg19: chr7-150752982; COSMIC: COSV52523827; COSMIC: COSV52523827;