14-99500873-TAAG-T

Position:

• chr14-99500873-TAAG-T

Variant summary

Our verdict is Likely benign. Variant got -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

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]

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 720140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 283 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC85C	NM_001144995.2	c.*14370_*14372delCTT		3_prime_UTR_variant	6/6	ENST00000380243.9	NP_001138467.1
CCNK	NM_001099402.2	c.517+8_517+10delGAA		splice_region_variant, intron_variant		ENST00000389879.9	NP_001092872.1
CCNK	XM_005268154.5	c.517+8_517+10delGAA		splice_region_variant, intron_variant			XP_005268211.1
CCNK	XM_047431839.1	c.517+8_517+10delGAA		splice_region_variant, intron_variant			XP_047287795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC85C	ENST00000380243	c.*14370_*14372delCTT		3_prime_UTR_variant	6/6	5	NM_001144995.2	ENSP00000369592.4
CCNK	ENST00000389879.9	c.517+8_517+10delGAA		splice_region_variant, intron_variant		5	NM_001099402.2	ENSP00000374529.5

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

GnomAD3 exomes AF: 0.00254 AC: 365 AN: 143442 Hom.: 3 AF XY: 0.00216 AC XY: 163 AN XY: 75530

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 SAS exome AF: 0.00

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

Gnomad4 AFR exome AF: 0.0000667

Gnomad4 AMR exome AF: 0.0149

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00198

Gnomad4 SAS exome AF: 0.0000403

Gnomad4 FIN exome AF: 0.0000202

Gnomad4 NFE exome AF: 0.0000498

Gnomad4 OTH exome AF: 0.000585

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

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000800 Hom.: 0

Bravo AF: 0.00329

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs201567868; hg19: chr14-99967210;