rs2069493

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_001099402.2(CCNK):​c.495A>T​(p.Leu165Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,548,782 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0038 (14 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (88 hom.)
• Consequence: CCNK NM_001099402.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 14-99500849-A-T is Benign according to our data. Variant chr14-99500849-A-T is described in ClinVar as Benign. ClinVar VariationId is 3039124.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.2 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00384 (585/152384) while in subpopulation AMR AF = 0.0238 (365/15304). AF 95% confidence interval is 0.0218. There are 14 homozygotes in GnomAd4. There are 337 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 585 Unknown,AD gene.

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>T	p.Leu165Leu	synonymous	Exon 5 of 11	NP_001092872.1	O75909-3
	CCDC85C	NM_001144995.2	MANE Select	c.*14397T>A		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>T	p.Leu165Leu	synonymous	Exon 5 of 11	ENSP00000374529.5	O75909-3
	CCNK	ENST00000555049.5	TSL:1	c.495A>T	p.Leu165Leu	synonymous	Exon 5 of 11	ENSP00000452307.1	G3V5E1
	CCDC85C	ENST00000380243.9	TSL:5 MANE Select	c.*14397T>A		3_prime_UTR	Exon 6 of 6	ENSP00000369592.4	A6NKD9

Frequencies

GnomAD3 genomes AF: 0.00386 AC: 587 AN: 152266 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.0192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00902 AC: 1464 AN: 162368 AF XY: 0.00741

Gnomad AFR exome AF: 0.000324

Gnomad AMR exome AF: 0.0464

Gnomad ASJ exome AF: 0.00566

Gnomad EAS exome AF: 0.0157

Gnomad FIN exome AF: 0.00418

Gnomad NFE exome AF: 0.000422

Gnomad OTH exome AF: 0.00536

GnomAD4 exome AF: 0.00268 AC: 3744 AN: 1396398 Hom.: 88 Cov.: 27 AF XY: 0.00251 AC XY: 1734 AN XY: 689562

African (AFR) AF: 0.000346 AC: 11 AN: 31758

American (AMR) AF: 0.0429 AC: 1498 AN: 34902

Ashkenazi Jewish (ASJ) AF: 0.00423 AC: 106 AN: 25064

East Asian (EAS) AF: 0.0415 AC: 1538 AN: 37056

South Asian (SAS) AF: 0.000336 AC: 26 AN: 77444

European-Finnish (FIN) AF: 0.00454 AC: 228 AN: 50194

Middle Eastern (MID) AF: 0.000528 AC: 3 AN: 5682

European-Non Finnish (NFE) AF: 0.000190 AC: 205 AN: 1076212

Other (OTH) AF: 0.00222 AC: 129 AN: 58086

GnomAD4 genome AF: 0.00384 AC: 585 AN: 152384 Hom.: 14 Cov.: 33 AF XY: 0.00452 AC XY: 337 AN XY: 74526

African (AFR) AF: 0.000481 AC: 20 AN: 41596

American (AMR) AF: 0.0238 AC: 365 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.0195 AC: 101 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00367 AC: 39 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68046

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00105 Hom.: 0

Bravo AF: 0.00529

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CCNK-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.71
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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; COSMIC: COSV66275476;