14-99500849-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. Synonymous variant affecting the same amino acid position (i.e. L165L) has been classified as Benign.

• 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
• Publications: 8 publications found

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

Our verdict: Likely_benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099402.2. 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
	CCNK	NM_001099402.2	MANE Select	c.495A>G	p.Leu165Leu	synonymous	Exon 5 of 11	NP_001092872.1	O75909-3
	CCDC85C	NM_001144995.2	MANE Select	c.*14397T>C		3_prime_UTR	Exon 6 of 6	NP_001138467.1	A6NKD9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNK	ENST00000389879.9	TSL:5 MANE Select	c.495A>G	p.Leu165Leu	synonymous	Exon 5 of 11	ENSP00000374529.5	O75909-3
	CCNK	ENST00000555049.5	TSL:1	c.495A>G	p.Leu165Leu	synonymous	Exon 5 of 11	ENSP00000452307.1	G3V5E1
	CCDC85C	ENST00000380243.9	TSL:5 MANE Select	c.*14397T>C		3_prime_UTR	Exon 6 of 6	ENSP00000369592.4	A6NKD9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 162368 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

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

African (AFR) AF: 0.00 AC: 0 AN: 31758

American (AMR) AF: 0.00 AC: 0 AN: 34920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25064

East Asian (EAS) AF: 0.00 AC: 0 AN: 37062

South Asian (SAS) AF: 0.00 AC: 0 AN: 77444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00000372 AC: 4 AN: 1076212

Other (OTH) AF: 0.00 AC: 0 AN: 58088

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.4
DANN	Benign	0.72
PhyloP100		1.2
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

Other links and lift over

dbSNP: rs2069493; hg19: chr14-99967186;