chr14-99502326-G-A

Variant names:

• chr14-99502326-G-A
• NM_001099402.2:c.695G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001099402.2(CCNK):​c.695G>A​(p.Arg232Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCNK NM_001099402.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.97

Genes affected

CCNK (HGNC:1596): (cyclin K) The protein encoded by this gene is a member of the transcription cyclin family. These cyclins may regulate transcription through their association with and activation of cyclin-dependent kinases (CDK) that phosphorylate the C-terminal domain (CTD) of the large subunit of RNA polymerase II. This gene product may play a dual role in regulating CDK and RNA polymerase II activities. [provided by RefSeq, Jul 2008]

CCDC85C (HGNC:35459): (coiled-coil domain containing 85C) Predicted to be involved in cerebral cortex development. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41883516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNK	NM_001099402.2	c.695G>A	p.Arg232Lys	missense_variant	Exon 7 of 11	ENST00000389879.9	NP_001092872.1
CCDC85C	NM_001144995.2	c.*12920C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000380243.9	NP_001138467.1
CCNK	XM_005268154.5	c.695G>A	p.Arg232Lys	missense_variant	Exon 7 of 11		XP_005268211.1
CCNK	XM_047431839.1	c.695G>A	p.Arg232Lys	missense_variant	Exon 8 of 12		XP_047287795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNK	ENST00000389879.9	c.695G>A	p.Arg232Lys	missense_variant	Exon 7 of 11	5	NM_001099402.2	ENSP00000374529.5
CCDC85C	ENST00000380243	c.*12920C>T		3_prime_UTR_variant	Exon 6 of 6	5	NM_001144995.2	ENSP00000369592.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.695G>A (p.R232K) alteration is located in exon 7 (coding exon 6) of the CCNK gene. This alteration results from a G to A substitution at nucleotide position 695, causing the arginine (R) at amino acid position 232 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-0.010
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.94	N;N
REVEL	Benign	0.21
Sift	Benign	0.25	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0070	B;.
Vest4		0.61
MutPred		0.50		Gain of methylation at R232 (P = 0.0121);Gain of methylation at R232 (P = 0.0121);
MVP		0.91
MPC		1.5
ClinPred		0.96	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-99968663;