rs201567868

Variant names:

• chr14-99500873-TAAG-T
• rs201567868
• NM_001144995.2:c.*14370_*14372delCTT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001099402.2(CCNK):​c.517+8_517+10delGAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000596 in 1,504,068 control chromosomes in the GnomAD database, including 7 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00045 (4 hom.)
• Consequence: CCNK NM_001099402.2 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.59
• Publications: 0 publications found

Genes affected

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]

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]

CCNK Gene-Disease associations (from GenCC):

• intellectual developmental disorder with hypertelorism and distinctive facies

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 14-99500873-TAAG-T is Benign according to our data. Variant chr14-99500873-TAAG-T is described in ClinVar as Benign. ClinVar VariationId is 720140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 283 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
	CCDC85C	NM_001144995.2	MANE Select	c.*14370_*14372delCTT		3_prime_UTR	Exon 6 of 6	NP_001138467.1	A6NKD9
	CCNK	NM_001099402.2	MANE Select	c.517+8_517+10delGAA		splice_region intron	N/A	NP_001092872.1	O75909-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC85C	ENST00000380243.9	TSL:5 MANE Select	c.*14370_*14372delCTT		3_prime_UTR	Exon 6 of 6	ENSP00000369592.4	A6NKD9
	CCNK	ENST00000389879.9	TSL:5 MANE Select	c.517+8_517+10delGAA		splice_region intron	N/A	ENSP00000374529.5	O75909-3
	CCNK	ENST00000555049.5	TSL:1	c.517+8_517+10delGAA		splice_region intron	N/A	ENSP00000452307.1	G3V5E1

Frequencies

GnomAD3 genomes AF: 0.00185 AC: 281 AN: 152228 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00254 AC: 365 AN: 143442 AF XY: 0.00216

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.0177

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000952

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000681

Gnomad OTH exome AF: 0.00268

GnomAD4 exome AF: 0.000453 AC: 613 AN: 1351722 Hom.: 4 AF XY: 0.000410 AC XY: 274 AN XY: 668816

African (AFR) AF: 0.0000667 AC: 2 AN: 29976

American (AMR) AF: 0.0149 AC: 449 AN: 30218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24494

East Asian (EAS) AF: 0.00198 AC: 71 AN: 35928

South Asian (SAS) AF: 0.0000403 AC: 3 AN: 74476

European-Finnish (FIN) AF: 0.0000202 AC: 1 AN: 49584

Middle Eastern (MID) AF: 0.000359 AC: 2 AN: 5572

European-Non Finnish (NFE) AF: 0.0000498 AC: 52 AN: 1045052

Other (OTH) AF: 0.000585 AC: 33 AN: 56422

GnomAD4 genome AF: 0.00186 AC: 283 AN: 152346 Hom.: 3 Cov.: 33 AF XY: 0.00234 AC XY: 174 AN XY: 74496

African (AFR) AF: 0.000289 AC: 12 AN: 41590

American (AMR) AF: 0.0162 AC: 248 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5186

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68024

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.000800 Hom.: 0

Bravo AF: 0.00329

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs201567868; hg19: chr14-99967210;