dbSNP rs9278: CDK5:c.*116G>A (chr7-151053893-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004935.4(CDK5):c.*116G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 857,168 control chromosomes in the GnomAD database, including 16,668 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 0.15 ( 2080 hom., cov: 32)

Exomes 𝑓: 0.19 ( 14588 hom. )

Consequence

CDK5
NM_004935.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.912

Publications

8 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5	NM_004935.4 link	c.*116G>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000485972.6	NP_004926.1	Q00535-1A0A090N7W4
CDK5	NM_001164410.3 link	c.*116G>A		3_prime_UTR_variant	Exon 11 of 11		NP_001157882.1	Q00535-2A0A0S2Z355

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5	ENST00000485972.6 link	c.*116G>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_004935.4	ENSP00000419782.1		Q00535-1
CDK5	ENST00000297518.4 link	c.*116G>A		downstream_gene_variant		1		ENSP00000297518.4		Q00535-2

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23106

AN:

152030

Hom.:

2081

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0768

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.0135

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.155

GnomAD4 exome

AF:

0.194

AC:

137027

AN:

705020

Hom.:

14588

Cov.:

AF XY:

0.197

AC XY:

70981

AN XY:

360922

show subpopulations

African (AFR)

AF:

0.0720

AC:

1226

AN:

17028

American (AMR)

AF:

0.107

AC:

2172

AN:

20276

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

2614

AN:

15930

East Asian (EAS)

AF:

0.0104

AC:

336

AN:

32240

South Asian (SAS)

AF:

0.243

AC:

13123

AN:

54078

European-Finnish (FIN)

AF:

0.146

AC:

5421

AN:

37240

Middle Eastern (MID)

AF:

0.203

AC:

507

AN:

2496

European-Non Finnish (NFE)

AF:

0.214

AC:

105382

AN:

491432

Other (OTH)

AF:

0.182

AC:

6246

AN:

34300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

5578

11157

16735

22314

27892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2414

4828

7242

9656

12070

<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:

0.152

AC:

23113

AN:

152148

Hom.:

2080

Cov.:

AF XY:

0.146

AC XY:

10895

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0767

AC:

3185

AN:

41542

American (AMR)

AF:

0.125

AC:

1910

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

580

AN:

3470

East Asian (EAS)

AF:

0.0135

AC:

AN:

5170

South Asian (SAS)

AF:

0.243

AC:

1173

AN:

4822

European-Finnish (FIN)

AF:

0.137

AC:

1456

AN:

10614

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14215

AN:

67928

Other (OTH)

AF:

0.157

AC:

332

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1003

2006

3008

4011

5014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<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:

0.178

Hom.:

985

Bravo

AF:

0.142

Asia WGS

AF:

0.138

AC:

483

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

0.71

(source)

DANN

Benign

0.57

PhyloP100

-0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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