dbSNP rs2069453: CDK5:c.313-326C>T (chr7-151056174-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004935.4(CDK5):c.313-326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 506,930 control chromosomes in the GnomAD database, including 3 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 0.0028 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00045 ( 1 hom. )

Consequence

CDK5
NM_004935.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.74

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

lissencephaly 7 with cerebellar hypoplasia
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

CDK5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5	NM_004935.4 link	c.313-326C>T		intron_variant	Intron 5 of 11	ENST00000485972.6	NP_004926.1	Q00535-1A0A090N7W4
CDK5	NM_001164410.3 link	c.312+406C>T		intron_variant	Intron 5 of 10		NP_001157882.1	Q00535-2A0A0S2Z355

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDK5	ENST00000485972.6 link	c.313-326C>T	intron_variant	Intron 5 of 11	1	NM_004935.4	ENSP00000419782.1	Q00535-1
CDK5	ENST00000297518.4 link	c.312+406C>T	intron_variant	Intron 5 of 10	1		ENSP00000297518.4	Q00535-2
CDK5	ENST00000476691.1 link	n.187C>T	non_coding_transcript_exon_variant	Exon 1 of 2	4
CDK5	ENST00000487703.5 link	n.677-326C>T	intron_variant	Intron 5 of 7	5

Frequencies

GnomAD3 genomes

AF:

0.00285

AC:

434

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00988

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00239

GnomAD4 exome

AF:

0.000451

AC:

160

AN:

354688

Hom.:

Cov.:

AF XY:

0.000385

AC XY:

AN XY:

184494

show subpopulations

African (AFR)

AF:

0.0105

AC:

116

AN:

11042

American (AMR)

AF:

0.000646

AC:

AN:

13934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11516

East Asian (EAS)

AF:

0.0000772

AC:

AN:

25918

South Asian (SAS)

AF:

0.0000629

AC:

AN:

31804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22928

Middle Eastern (MID)

AF:

0.000619

AC:

AN:

1616

European-Non Finnish (NFE)

AF:

0.0000885

AC:

AN:

214598

Other (OTH)

AF:

0.000516

AC:

AN:

21332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00284

AC:

433

AN:

152242

Hom.:

Cov.:

AF XY:

0.00270

AC XY:

201

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00983

AC:

408

AN:

41518

American (AMR)

AF:

0.000785

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68028

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00331

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.014

(source)

DANN

Benign

0.61

PhyloP100

-2.7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over