Variant 7-92609830-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001145306.2(CDK6):c.*5310T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 230,198 control chromosomes in the GnomAD database, including 5,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.19 ( 3303 hom., cov: 32)

Exomes 𝑓: 0.22 ( 2088 hom. )

Consequence

CDK6
NM_001145306.2 3_prime_UTR

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 0.370

Variant links:

Genes affected

CDK6 (HGNC:1777): (cyclin dependent kinase 6) The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. Altered expression of this gene has been observed in multiple human cancers. A mutation in this gene resulting in reduced cell proliferation, and impaired cell motility and polarity, and has been identified in patients with primary microcephaly. [provided by RefSeq, Aug 2017]

CDK6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
CDK6	NM_001145306.2 linkuse as main transcript	c.*5310T>C	3_prime_UTR_variant	8/8	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8 linkuse as main transcript	c.*5310T>C	3_prime_UTR_variant	8/8		NP_001250.1
CDK6	XM_047419716.1 linkuse as main transcript	c.*5310T>C	3_prime_UTR_variant	8/8		XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK6	ENST00000424848.3 linkuse as main transcript	c.*5310T>C		3_prime_UTR_variant	8/8	1	NM_001145306.2	ENSP00000397087	P1
CDK6	ENST00000265734.8 linkuse as main transcript	c.*5310T>C		3_prime_UTR_variant	8/8	1		ENSP00000265734	P1

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29268

AN:

152026

Hom.:

3308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0833

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.226

GnomAD4 exome

AF:

0.221

AC:

17277

AN:

78054

Hom.:

2088

Cov.:

AF XY:

0.222

AC XY:

7978

AN XY:

35932

show subpopulations

Gnomad4 AFR exome

AF:

0.0831

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.291

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.293

Gnomad4 NFE exome

AF:

0.248

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.192

AC:

29261

AN:

152144

Hom.:

3303

Cov.:

AF XY:

0.192

AC XY:

14253

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0832

Gnomad4 AMR

AF:

0.215

Gnomad4 ASJ

AF:

0.295

Gnomad4 EAS

AF:

0.103

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.229

Gnomad4 NFE

AF:

0.252

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.223

Hom.:

1163

Bravo

AF:

0.190

Asia WGS

AF:

0.133

AC:

462

AN:

3474

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Behcet disease

Other:1

association, no assertion criteria provided

case-control

Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University

Nov 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.4

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over