16-89686715-C-A

Variant names:

• chr16-89686715-C-A
• rs746422526
• NM_052988.5:c.5C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052988.5(CDK10):​c.5C>A​(p.Ala2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,447,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A2T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CDK10 NM_052988.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18712676).

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.5C>A	p.Ala2Glu	missense	Exon 1 of 13	NP_443714.3
	CDK10	NM_001160367.2		c.-171C>A		5_prime_UTR	Exon 1 of 13	NP_001153839.1	Q15131-2
	CDK10	NM_001098533.3		c.-171C>A		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.5C>A	p.Ala2Glu	missense	Exon 1 of 13	ENSP00000338673.7	Q15131-1
	CDK10	ENST00000505473.5	TSL:1	c.-171C>A		5_prime_UTR	Exon 1 of 13	ENSP00000424415.1	Q15131-4
	CDK10	ENST00000851882.1		c.5C>A	p.Ala2Glu	missense	Exon 1 of 13	ENSP00000521941.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000414 AC: 6 AN: 1447894 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 719336

African (AFR) AF: 0.0000303 AC: 1 AN: 33016

American (AMR) AF: 0.00 AC: 0 AN: 43198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25836

East Asian (EAS) AF: 0.00 AC: 0 AN: 38540

South Asian (SAS) AF: 0.00 AC: 0 AN: 84104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00000452 AC: 5 AN: 1106048

Other (OTH) AF: 0.00 AC: 0 AN: 59768

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.48	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.081
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.014	D
Polyphen		0.11	B
Vest4		0.34
MutPred		0.18		Gain of disorder (P = 0.0285)
MVP		0.51
MPC		0.12
ClinPred		0.21	T
GERP RS		-1.4
PromoterAI		-0.39	Neutral
Varity_R		0.13
gMVP		0.61
Mutation Taster		=293/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs746422526; hg19: chr16-89753123;