12-96297725-C-A

Variant names:

• chr12-96297725-C-A
• rs141560239
• NM_002595.5:c.716-4G>T

Variant summary

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

The NM_002595.5(CDK17):​c.716-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000297 in 1,346,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: CDK17 NM_002595.5 splice_region, intron
• Scores: Splicing: ADA: 0.00007784
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 0 publications found

Genes affected

CDK17 (HGNC:8750): (cyclin dependent kinase 17) The protein encoded by this gene belongs to the cdc2/cdkx subfamily of the ser/thr family of protein kinases. It has similarity to a rat protein that is thought to play a role in terminally differentiated neurons. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Jul 2010]

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 (BayesDel_noAF=-0.45).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002595.5. 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
	CDK17	NM_002595.5	MANE Select	c.716-4G>T		splice_region intron	N/A	NP_002586.2
	CDK17	NM_001170464.4		c.716-4G>T		splice_region intron	N/A	NP_001163935.1	Q00537-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK17	ENST00000261211.8	TSL:1 MANE Select	c.716-4G>T		splice_region intron	N/A	ENSP00000261211.3	Q00537-1
	CDK17	ENST00000859519.1		c.716-4G>T		splice_region intron	N/A	ENSP00000529578.1
	CDK17	ENST00000964179.1		c.716-4G>T		splice_region intron	N/A	ENSP00000634238.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000841 AC: 2 AN: 237842 AF XY: 0.00000774

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: 0.00000911

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000297 AC: 4 AN: 1346368 Hom.: 0 Cov.: 20 AF XY: 0.00000148 AC XY: 1 AN XY: 675102

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30232

American (AMR) AF: 0.00 AC: 0 AN: 39454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24792

East Asian (EAS) AF: 0.00 AC: 0 AN: 38992

South Asian (SAS) AF: 0.0000245 AC: 2 AN: 81570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5484

European-Non Finnish (NFE) AF: 0.00000197 AC: 2 AN: 1016378

Other (OTH) AF: 0.00 AC: 0 AN: 56316

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0332287), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000121 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.0
DANN	Benign	0.72
PhyloP100		-1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000078
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs141560239; hg19: chr12-96691503;