Variant 9-120389401-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018249.6(CDK5RAP2):c.5626-109T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 866,718 control chromosomes in the GnomAD database, including 236,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45243 hom., cov: 33)

Exomes 𝑓: 0.73 ( 191015 hom. )

Consequence

CDK5RAP2
NM_018249.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.106

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 9-120389401-A-G is Benign according to our data. Variant chr9-120389401-A-G is described in ClinVar as [Benign]. Clinvar id is 678323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 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.5626-109T>C		intron_variant		ENST00000349780.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK5RAP2	ENST00000349780.9 linkuse as main transcript	c.5626-109T>C		intron_variant		1	NM_018249.6	P4	Q96SN8-1

Frequencies

GnomAD3 genomes

AF:

0.768

AC:

116737

AN:

152100

Hom.:

45182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.856

Gnomad AMI

AF:

0.693

Gnomad AMR

AF:

0.780

Gnomad ASJ

AF:

0.677

Gnomad EAS

AF:

0.843

Gnomad SAS

AF:

0.676

Gnomad FIN

AF:

0.820

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.710

Gnomad OTH

AF:

0.754

GnomAD4 exome

AF:

0.729

AC:

520877

AN:

714500

Hom.:

191015

AF XY:

0.725

AC XY:

273336

AN XY:

376966

show subpopulations

Gnomad4 AFR exome

AF:

0.859

Gnomad4 AMR exome

AF:

0.814

Gnomad4 ASJ exome

AF:

0.683

Gnomad4 EAS exome

AF:

0.865

Gnomad4 SAS exome

AF:

0.676

Gnomad4 FIN exome

AF:

0.804

Gnomad4 NFE exome

AF:

0.711

Gnomad4 OTH exome

AF:

0.735

GnomAD4 genome

AF:

0.768

AC:

116857

AN:

152218

Hom.:

45243

Cov.:

AF XY:

0.771

AC XY:

57341

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.856

Gnomad4 AMR

AF:

0.781

Gnomad4 ASJ

AF:

0.677

Gnomad4 EAS

AF:

0.843

Gnomad4 SAS

AF:

0.675

Gnomad4 FIN

AF:

0.820

Gnomad4 NFE

AF:

0.710

Gnomad4 OTH

AF:

0.757

Alfa

AF:

0.735

Hom.:

10574

Bravo

AF:

0.774

Asia WGS

AF:

0.816

AC:

2838

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.73

CADD

Benign

DANN

Benign

0.76

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