16-89686751-A-G

Variant names:

• chr16-89686751-A-G
• rs1258010770
• NM_052988.5:c.41A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_052988.5(CDK10):​c.41A>G​(p.Lys14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CDK10 NM_052988.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052988.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK10	NM_052988.5	MANE Select	c.41A>G	p.Lys14Arg	missense	Exon 1 of 13	NP_443714.3
	CDK10	NM_001160367.2		c.-135A>G		5_prime_UTR	Exon 1 of 13	NP_001153839.1	Q15131-2
	CDK10	NM_001098533.3		c.-135A>G		5_prime_UTR	Exon 1 of 13	NP_001092003.2	Q15131-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK10	ENST00000353379.12	TSL:1 MANE Select	c.41A>G	p.Lys14Arg	missense	Exon 1 of 13	ENSP00000338673.7	Q15131-1
	CDK10	ENST00000505473.5	TSL:1	c.-135A>G		5_prime_UTR	Exon 1 of 13	ENSP00000424415.1	Q15131-4
	CDK10	ENST00000851882.1		c.41A>G	p.Lys14Arg	missense	Exon 1 of 13	ENSP00000521941.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000818 AC: 2 AN: 244580 AF XY: 0.00000749

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

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: 0.000168

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460284 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726450

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.0000448 AC: 2 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 86138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111220

Other (OTH) AF: 0.00 AC: 0 AN: 60290

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.0
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.042
Sift	Benign	0.45	T
Sift4G	Benign	0.38	T
Polyphen		0.047	B
Vest4		0.30
MutPred		0.35		Loss of methylation at K14 (P = 0.0089)
MVP		0.50
MPC		0.082
ClinPred		0.24	T
GERP RS		4.5
PromoterAI		0.017	Neutral
Varity_R		0.12
gMVP		0.53
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.47		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.47		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1258010770; hg19: chr16-89753159;