Variant rs74691300 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018249.6(CDK5RAP2):c.3025+48G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 1,316,414 control chromosomes in the GnomAD database, including 536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 51 hom., cov: 32)

Exomes 𝑓: 0.026 ( 485 hom. )

Consequence

CDK5RAP2
NM_018249.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.61

Variant links:

Genes affected

CDK5RAP2 (HGNC:18672): (CDK5 regulatory subunit associated protein 2) This gene encodes a regulator of CDK5 (cyclin-dependent kinase 5) activity. The protein encoded by this gene is localized to the centrosome and Golgi complex, interacts with CDK5R1 and pericentrin (PCNT), plays a role in centriole engagement and microtubule nucleation, and has been linked to primary microcephaly and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

CDK5RAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

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

BP6

Variant 9-120447847-C-A is Benign according to our data. Variant chr9-120447847-C-A is described in ClinVar as [Benign]. Clinvar id is 158136.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK5RAP2	NM_018249.6 linkuse as main transcript	c.3025+48G>T		intron_variant		ENST00000349780.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK5RAP2	ENST00000349780.9 linkuse as main transcript	c.3025+48G>T		intron_variant		1	NM_018249.6	P4	Q96SN8-1

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3370

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00982

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.0410

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.0414

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.0272

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0231

AC:

5789

AN:

250492

Hom.:

106

AF XY:

0.0226

AC XY:

3062

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.00886

Gnomad AMR exome

AF:

0.0126

Gnomad ASJ exome

AF:

0.0143

Gnomad EAS exome

AF:

0.0378

Gnomad SAS exome

AF:

0.00696

Gnomad FIN exome

AF:

0.0382

Gnomad NFE exome

AF:

0.0280

Gnomad OTH exome

AF:

0.0276

GnomAD4 exome

AF:

0.0265

AC:

30812

AN:

1164100

Hom.:

485

Cov.:

AF XY:

0.0256

AC XY:

15221

AN XY:

593792

show subpopulations

Gnomad4 AFR exome

AF:

0.00913

Gnomad4 AMR exome

AF:

0.0124

Gnomad4 ASJ exome

AF:

0.0150

Gnomad4 EAS exome

AF:

0.0693

Gnomad4 SAS exome

AF:

0.00721

Gnomad4 FIN exome

AF:

0.0360

Gnomad4 NFE exome

AF:

0.0274

Gnomad4 OTH exome

AF:

0.0251

GnomAD4 genome

AF:

0.0221

AC:

3372

AN:

152314

Hom.:

Cov.:

AF XY:

0.0226

AC XY:

1682

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00979

Gnomad4 AMR

AF:

0.0141

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.0411

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.0414

Gnomad4 NFE

AF:

0.0272

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.0210

Asia WGS

AF:

0.0360

AC:

126

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.094

DANN

Benign

0.79

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