Variant 9-120394379-T-G 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.5578+133A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,401,658 control chromosomes in the GnomAD database, including 97,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 8431 hom., cov: 32)

Exomes 𝑓: 0.37 ( 89273 hom. )

Consequence

CDK5RAP2
NM_018249.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.31

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=-0.86).

BP6

Variant 9-120394379-T-G is Benign according to our data. Variant chr9-120394379-T-G is described in ClinVar as [Benign]. Clinvar id is 678330.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK5RAP2	NM_018249.6 linkuse as main transcript	c.5578+133A>C		intron_variant		ENST00000349780.9	NP_060719.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK5RAP2	ENST00000349780.9 linkuse as main transcript	c.5578+133A>C		intron_variant		1	NM_018249.6	ENSP00000343818	P4	Q96SN8-1

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45805

AN:

151888

Hom.:

8421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0895

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.446

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.482

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.313

GnomAD4 exome

AF:

0.371

AC:

464201

AN:

1249652

Hom.:

89273

AF XY:

0.374

AC XY:

235338

AN XY:

629390

show subpopulations

Gnomad4 AFR exome

AF:

0.0762

Gnomad4 AMR exome

AF:

0.492

Gnomad4 ASJ exome

AF:

0.316

Gnomad4 EAS exome

AF:

0.439

Gnomad4 SAS exome

AF:

0.454

Gnomad4 FIN exome

AF:

0.461

Gnomad4 NFE exome

AF:

0.365

Gnomad4 OTH exome

AF:

0.348

GnomAD4 genome

AF:

0.301

AC:

45824

AN:

152006

Hom.:

8431

Cov.:

AF XY:

0.311

AC XY:

23107

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0894

Gnomad4 AMR

AF:

0.394

Gnomad4 ASJ

AF:

0.302

Gnomad4 EAS

AF:

0.445

Gnomad4 SAS

AF:

0.466

Gnomad4 FIN

AF:

0.482

Gnomad4 NFE

AF:

0.359

Gnomad4 OTH

AF:

0.315

Alfa

AF:

0.251

Hom.:

948

Bravo

AF:

0.288

Asia WGS

AF:

0.420

AC:

1459

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.66

DANN

Benign

0.69

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