Genetic Variant CDK5:c.650+48A>G (chr7-151054979-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004935.4(CDK5):c.650+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,589,312 control chromosomes in the GnomAD database, including 584,574 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 0.88 ( 59517 hom., cov: 31)

Exomes 𝑓: 0.85 ( 525057 hom. )

Consequence

CDK5
NM_004935.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.47

Variant links:

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]

CDK5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5	NM_004935.4 link	c.650+48A>G		intron_variant	Intron 9 of 11	ENST00000485972.6	NP_004926.1	Q00535-1A0A090N7W4
CDK5	NM_001164410.3 link	c.554+48A>G		intron_variant	Intron 8 of 10		NP_001157882.1	Q00535-2A0A0S2Z355

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5	ENST00000485972.6 link	c.650+48A>G		intron_variant	Intron 9 of 11	1	NM_004935.4	ENSP00000419782.1		Q00535-1
CDK5	ENST00000297518.4 link	c.554+48A>G		intron_variant	Intron 8 of 10	1		ENSP00000297518.4		Q00535-2

Frequencies

GnomAD3 genomes

AF:

0.883

AC:

134353

AN:

152090

Hom.:

59460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.940

Gnomad AMI

AF:

0.845

Gnomad AMR

AF:

0.900

Gnomad ASJ

AF:

0.907

Gnomad EAS

AF:

0.956

Gnomad SAS

AF:

0.843

Gnomad FIN

AF:

0.863

Gnomad MID

AF:

0.924

Gnomad NFE

AF:

0.845

Gnomad OTH

AF:

0.883

GnomAD3 exomes

AF:

0.876

AC:

215506

AN:

245886

Hom.:

94637

AF XY:

0.870

AC XY:

116237

AN XY:

133604

show subpopulations

Gnomad AFR exome

AF:

0.945

Gnomad AMR exome

AF:

0.934

Gnomad ASJ exome

AF:

0.901

Gnomad EAS exome

AF:

0.958

Gnomad SAS exome

AF:

0.851

Gnomad FIN exome

AF:

0.866

Gnomad NFE exome

AF:

0.843

Gnomad OTH exome

AF:

0.874

GnomAD4 exome

AF:

0.854

AC:

1227323

AN:

1437104

Hom.:

525057

Cov.:

AF XY:

0.853

AC XY:

611160

AN XY:

716274

show subpopulations

Gnomad4 AFR exome

AF:

0.943

Gnomad4 AMR exome

AF:

0.931

Gnomad4 ASJ exome

AF:

0.900

Gnomad4 EAS exome

AF:

0.972

Gnomad4 SAS exome

AF:

0.851

Gnomad4 FIN exome

AF:

0.864

Gnomad4 NFE exome

AF:

0.842

Gnomad4 OTH exome

AF:

0.866

GnomAD4 genome

AF:

0.883

AC:

134469

AN:

152208

Hom.:

59517

Cov.:

AF XY:

0.883

AC XY:

65732

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.940

Gnomad4 AMR

AF:

0.900

Gnomad4 ASJ

AF:

0.907

Gnomad4 EAS

AF:

0.956

Gnomad4 SAS

AF:

0.843

Gnomad4 FIN

AF:

0.863

Gnomad4 NFE

AF:

0.845

Gnomad4 OTH

AF:

0.885

Alfa

AF:

0.867

Hom.:

14639

Bravo

AF:

0.891

Asia WGS

AF:

0.914

AC:

3178

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.0090

DANN

Benign

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over