Variant NM_004935.4:c.*5C>T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004935.4(CDK5):c.*5C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00083 in 1,582,692 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 19 hom. )

Consequence

CDK5
NM_004935.4 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.30

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-151054004-G-A is Benign according to our data. Variant chr7-151054004-G-A is described in ClinVar as [Benign]. Clinvar id is 3037340.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00118 (179/152252) while in subpopulation EAS AF= 0.0267 (138/5172). AF 95% confidence interval is 0.0231. There are 4 homozygotes in gnomad4. There are 102 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5	NM_004935.4 link	c.*5C>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000485972.6	NP_004926.1	Q00535-1A0A090N7W4
CDK5	NM_001164410.3 link	c.*5C>T		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 link	c.*5C>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_004935.4	ENSP00000419782.1		Q00535-1
CDK5	ENST00000297518.4 link	c.*5C>T		downstream_gene_variant		1		ENSP00000297518.4		Q00535-2

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

180

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.0266

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00256

AC:

504

AN:

197196

Hom.:

AF XY:

0.00265

AC XY:

282

AN XY:

106486

show subpopulations

Gnomad AFR exome

AF:

0.0000892

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00672

Gnomad EAS exome

AF:

0.0291

Gnomad SAS exome

AF:

0.000156

Gnomad FIN exome

AF:

0.0000586

Gnomad NFE exome

AF:

0.0000818

Gnomad OTH exome

AF:

0.000974

GnomAD4 exome

AF:

0.000793

AC:

1135

AN:

1430440

Hom.:

Cov.:

AF XY:

0.000821

AC XY:

582

AN XY:

708508

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.0000505

Gnomad4 ASJ exome

AF:

0.00575

Gnomad4 EAS exome

AF:

0.0218

Gnomad4 SAS exome

AF:

0.000269

Gnomad4 FIN exome

AF:

0.0000589

Gnomad4 NFE exome

AF:

0.0000456

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00118

AC:

179

AN:

152252

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.0267

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000535

Hom.:

Bravo

AF:

0.00155

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CDK5-related disorder

Benign:1

May 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.2

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over