rs2069493

Variant names:

• chr14-99500849-A-G
• rs2069493
• NM_001099402.2:c.495A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-99500849-A-G
• chr14-99500849-A-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001099402.2(CCNK):​c.495A>G​(p.Leu165Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,396,424 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: CCNK NM_001099402.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=1.2 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNK	NM_001099402.2	c.495A>G	p.Leu165Leu	synonymous_variant	Exon 5 of 11	ENST00000389879.9	NP_001092872.1
CCDC85C	NM_001144995.2	c.*14397T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000380243.9	NP_001138467.1
CCNK	XM_005268154.5	c.495A>G	p.Leu165Leu	synonymous_variant	Exon 5 of 11		XP_005268211.1
CCNK	XM_047431839.1	c.495A>G	p.Leu165Leu	synonymous_variant	Exon 6 of 12		XP_047287795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNK	ENST00000389879.9	c.495A>G	p.Leu165Leu	synonymous_variant	Exon 5 of 11	5	NM_001099402.2	ENSP00000374529.5
CCDC85C	ENST00000380243	c.*14397T>C		3_prime_UTR_variant	Exon 6 of 6	5	NM_001144995.2	ENSP00000369592.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1396424 Hom.: 0 Cov.: 27 AF XY: 0.00000145 AC XY: 1 AN XY: 689572

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000372

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.4
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs2069493; hg19: chr14-99967186;