Genetic Variant CDK10:p.Pro4Thr (chr16-89686720-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052988.5(CDK10):c.10C>A(p.Pro4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,451,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CDK10
NM_052988.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.166

Publications

4 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058751225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK10	NM_052988.5 link	c.10C>A	p.Pro4Thr	missense_variant	Exon 1 of 13	ENST00000353379.12	NP_443714.3	Q15131-1B7Z537

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK10	ENST00000353379.12 link	c.10C>A	p.Pro4Thr	missense_variant	Exon 1 of 13	1	NM_052988.5	ENSP00000338673.7		Q15131-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000436

AC:

AN:

229474

AF XY:

0.00000797

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1451834

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721552

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33162

American (AMR)

AF:

0.00

AC:

AN:

43794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25904

East Asian (EAS)

AF:

0.00

AC:

AN:

38954

South Asian (SAS)

AF:

0.0000472

AC:

AN:

84746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52040

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107638

Other (OTH)

AF:

0.00

AC:

AN:

59928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.6

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.064

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.

PhyloP100

0.17

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.79

N;.

REVEL

Benign

0.076

Sift

Benign

0.26

T;.

Sift4G

Benign

0.22

T;D

Polyphen

0.0

B;.

Vest4

0.24

MutPred

0.25

Loss of disorder (P = 0.069);Loss of disorder (P = 0.069);

MVP

0.49

MPC

0.11

ClinPred

0.026

GERP RS

2.2

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.032

gMVP

0.54

Mutation Taster

=99/1

polymorphism

(source)

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

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16-89686720-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over