dbSNP rs932975: CDK5RAP2:c.-3G>T (chr9-120579981-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_018249.6(CDK5RAP2):c.-3G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,607,410 control chromosomes in the GnomAD database, including 796,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 73013 hom., cov: 36)

Exomes 𝑓: 1.0 ( 723320 hom. )

Consequence

CDK5RAP2
NM_018249.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.357

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 9-120579981-C-A is Benign according to our data. Variant chr9-120579981-C-A is described in ClinVar as [Benign]. Clinvar id is 95896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-120579981-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5RAP2	NM_018249.6 link	c.-3G>T		5_prime_UTR_variant	Exon 1 of 38	ENST00000349780.9	NP_060719.4	Q96SN8-1B3KVI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5RAP2	ENST00000349780.9 link	c.-3G>T		5_prime_UTR_variant	Exon 1 of 38	1	NM_018249.6	ENSP00000343818.4		Q96SN8-1

Frequencies

GnomAD3 genomes

AF:

0.979

AC:

148989

AN:

152236

Hom.:

72971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.929

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.989

Gnomad ASJ

AF:

0.996

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.984

GnomAD3 exomes

AF:

0.993

AC:

247017

AN:

248680

Hom.:

122723

AF XY:

0.995

AC XY:

134159

AN XY:

134870

show subpopulations

Gnomad AFR exome

AF:

0.924

Gnomad AMR exome

AF:

0.994

Gnomad ASJ exome

AF:

0.997

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.994

GnomAD4 exome

AF:

0.997

AC:

1450731

AN:

1455056

Hom.:

723320

Cov.:

AF XY:

0.997

AC XY:

722460

AN XY:

724426

show subpopulations

Gnomad4 AFR exome

AF:

0.926

Gnomad4 AMR exome

AF:

0.993

Gnomad4 ASJ exome

AF:

0.998

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.994

GnomAD4 genome

AF:

0.979

AC:

149089

AN:

152354

Hom.:

73013

Cov.:

AF XY:

0.979

AC XY:

72947

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.928

Gnomad4 AMR

AF:

0.989

Gnomad4 ASJ

AF:

0.996

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.984

Alfa

AF:

0.991

Hom.:

26446

Bravo

AF:

0.975

Asia WGS

AF:

0.993

AC:

3455

AN:

3478

EpiCase

AF:

0.998

EpiControl

AF:

0.998

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Jul 03, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Microcephaly 3, primary, autosomal recessive

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 31, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary Microcephaly, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

5.3

DANN

Benign

0.63

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