16-89689495-A-G

Variant names:

• chr16-89689495-A-G
• rs258322
• NM_052988.5:c.160+171A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052988.5(CDK10):​c.160+171A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 618,936 control chromosomes in the GnomAD database, including 232,131 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.85 (55487 hom., cov: 32)
  • Exomes 𝑓: 0.86 (176644 hom.)
• Consequence: CDK10 NM_052988.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 104 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]

CDK10 Gene-Disease associations (from GenCC):

• Al Kaissi syndrome

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK10	NM_052988.5	MANE Select	c.160+171A>G		intron	N/A	NP_443714.3
	CDK10	NM_001160367.2		c.-54+171A>G		intron	N/A	NP_001153839.1
	CDK10	NM_001098533.3		c.-54+171A>G		intron	N/A	NP_001092003.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK10	ENST00000353379.12	TSL:1 MANE Select	c.160+171A>G		intron	N/A	ENSP00000338673.7
	CDK10	ENST00000505473.5	TSL:1	c.-54+171A>G		intron	N/A	ENSP00000424415.1
	CDK10	ENST00000625631.1	TSL:1	c.88-1058A>G		intron	N/A	ENSP00000486594.1

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128966 AN: 152004 Hom.: 55469 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.876

GnomAD4 exome AF: 0.860 AC: 401430 AN: 466812 Hom.: 176644 Cov.: 5 AF XY: 0.865 AC XY: 212032 AN XY: 245168

African (AFR) AF: 0.803 AC: 10407 AN: 12958

American (AMR) AF: 0.839 AC: 17603 AN: 20982

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 12995 AN: 14226

East Asian (EAS) AF: 0.398 AC: 12226 AN: 30702

South Asian (SAS) AF: 0.920 AC: 43340 AN: 47090

European-Finnish (FIN) AF: 0.831 AC: 35020 AN: 42158

Middle Eastern (MID) AF: 0.950 AC: 1893 AN: 1992

European-Non Finnish (NFE) AF: 0.907 AC: 245460 AN: 270508

Other (OTH) AF: 0.858 AC: 22486 AN: 26196

GnomAD4 genome AF: 0.848 AC: 129031 AN: 152124 Hom.: 55487 Cov.: 32 AF XY: 0.844 AC XY: 62724 AN XY: 74356

African (AFR) AF: 0.802 AC: 33274 AN: 41490

American (AMR) AF: 0.851 AC: 12975 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3147 AN: 3472

East Asian (EAS) AF: 0.394 AC: 2036 AN: 5164

South Asian (SAS) AF: 0.905 AC: 4362 AN: 4822

European-Finnish (FIN) AF: 0.828 AC: 8765 AN: 10582

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.904 AC: 61483 AN: 68024

Other (OTH) AF: 0.873 AC: 1841 AN: 2110

Alfa AF: 0.882 Hom.: 255951

Bravo AF: 0.842

Asia WGS AF: 0.662 AC: 2306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.6
DANN	Benign	0.36
PhyloP100		-0.079
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs258322; hg19: chr16-89755903;