Variant 16-89686720-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_052988.5(CDK10):c.10C>G(p.Pro4Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00533 in 1,603,842 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 34)

Exomes 𝑓: 0.0054 ( 31 hom. )

Consequence

CDK10
NM_052988.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.166

Variant links:

Genes affected

CDK10 (HGNC:1770): (cyclin dependent kinase 10) The protein encoded by this gene belongs to the CDK subfamily of the Ser/Thr protein kinase family. The CDK subfamily members are highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, and are known to be essential for cell cycle progression. This kinase has been shown to play a role in cellular proliferation and its function is limited to cell cycle G2-M phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

CDK10 links:

LINC02166 (HGNC:53027): (long intergenic non-protein coding RNA 2166)

LINC02166 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035604239).

BP6

Variant 16-89686720-C-G is Benign according to our data. Variant chr16-89686720-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2570957.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00433 (658/152078) while in subpopulation NFE AF= 0.0067 (455/67862). AF 95% confidence interval is 0.0062. There are 3 homozygotes in gnomad4. There are 306 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK10	NM_052988.5 link	c.10C>G	p.Pro4Ala	missense_variant	1/13	ENST00000353379.12	NP_443714.3	Q15131-1B7Z537

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK10	ENST00000353379.12 link	c.10C>G	p.Pro4Ala	missense_variant	1/13	1	NM_052988.5	ENSP00000338673.7		Q15131-1

Frequencies

GnomAD3 genomes

AF:

0.00434

AC:

659

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00536

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00425

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00670

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00414

AC:

950

AN:

229474

Hom.:

AF XY:

0.00421

AC XY:

528

AN XY:

125424

show subpopulations

Gnomad AFR exome

AF:

0.0000734

Gnomad AMR exome

AF:

0.00325

Gnomad ASJ exome

AF:

0.00487

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00249

Gnomad FIN exome

AF:

0.00421

Gnomad NFE exome

AF:

0.00604

Gnomad OTH exome

AF:

0.00409

GnomAD4 exome

AF:

0.00544

AC:

7894

AN:

1451764

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

3960

AN XY:

721520

show subpopulations

Gnomad4 AFR exome

AF:

0.000452

Gnomad4 AMR exome

AF:

0.00304

Gnomad4 ASJ exome

AF:

0.00556

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00230

Gnomad4 FIN exome

AF:

0.00590

Gnomad4 NFE exome

AF:

0.00610

Gnomad4 OTH exome

AF:

0.00536

GnomAD4 genome

AF:

0.00433

AC:

658

AN:

152078

Hom.:

Cov.:

AF XY:

0.00412

AC XY:

306

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00529

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00425

Gnomad4 NFE

AF:

0.00670

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00644

Hom.:

Bravo

AF:

0.00408

ESP6500AA

AF:

0.000257

AC:

ESP6500EA

AF:

0.00507

AC:

ExAC

AF:

0.00375

AC:

450

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

CDK10: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.5

DANN

Benign

0.97

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0036

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.2

N;.

REVEL

Benign

0.055

Sift

Benign

0.68

T;.

Sift4G

Benign

0.27

T;D

Polyphen

0.0

B;.

Vest4

0.23

MVP

0.39

MPC

0.098

ClinPred

0.011

GERP RS

2.2

Varity_R

0.016

gMVP

0.43

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