16-89686720-C-G

Position:

• chr16-89686720-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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 (★). Synonymous variant affecting the same amino acid position (i.e. P4P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0043 (3 hom., cov: 34)
  • Exomes 𝑓: 0.0054 (31 hom.)
• Consequence: CDK10 NM_052988.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.166

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]

LINC02166 (HGNC:):

ACMG classification

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	UniProt
CDK10	NM_052988.5	c.10C>G	p.Pro4Ala	missense_variant	1/13	ENST00000353379.12
LINC02166	NR_184150.1	n.193G>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK10	ENST00000353379.12	c.10C>G	p.Pro4Ala	missense_variant	1/13	1	NM_052988.5	P1

Frequencies

GnomAD3 genomes AF: 0.00434 AC: 659 AN: 151960 Hom.: 3 Cov.: 34

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.: 5 AF XY: 0.00421 AC XY: 528 AN XY: 125424

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.: 31 Cov.: 31 AF XY: 0.00549 AC XY: 3960 AN XY: 721520

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.: 3 Cov.: 34 AF XY: 0.00412 AC XY: 306 AN XY: 74354

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.: 2

Bravo AF: 0.00408

ESP6500AA AF: 0.000257 AC: 1

ESP6500EA AF: 0.00507 AC: 42

ExAC AF: 0.00375 AC: 450

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 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	T
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	N
LIST_S2	Benign	0.57	T;T
MetaRNN	Benign	0.0036	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.48	T
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	T
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

Other links and lift over

dbSNP: rs187319559; hg19: chr16-89753128;