Variant 7-92618225-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001145306.2(CDK6):c.699-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 1,613,104 control chromosomes in the GnomAD database, including 2,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 181 hom., cov: 32)

Exomes 𝑓: 0.052 ( 2156 hom. )

Consequence

CDK6
NM_001145306.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0160

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 7-92618225-A-G is Benign according to our data. Variant chr7-92618225-A-G is described in ClinVar as [Benign]. Clinvar id is 1226582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CDK6	NM_001145306.2 linkuse as main transcript	c.699-18T>C	intron_variant	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8 linkuse as main transcript	c.699-18T>C	intron_variant		NP_001250.1
CDK6	XM_047419716.1 linkuse as main transcript	c.699-18T>C	intron_variant		XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
CDK6	ENST00000424848.3 linkuse as main transcript	c.699-18T>C	intron_variant		1	NM_001145306.2	ENSP00000397087	P1
CDK6	ENST00000265734.8 linkuse as main transcript	c.699-18T>C	intron_variant		1		ENSP00000265734	P1
CDK6	ENST00000467166.1 linkuse as main transcript	n.53T>C	non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0425

AC:

6471

AN:

152192

Hom.:

182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0201

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0375

Gnomad ASJ

AF:

0.0848

Gnomad EAS

AF:

0.00655

Gnomad SAS

AF:

0.0325

Gnomad FIN

AF:

0.0446

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0583

Gnomad OTH

AF:

0.0483

GnomAD3 exomes

AF:

0.0458

AC:

11479

AN:

250714

Hom.:

325

AF XY:

0.0470

AC XY:

6374

AN XY:

135494

show subpopulations

Gnomad AFR exome

AF:

0.0197

Gnomad AMR exome

AF:

0.0266

Gnomad ASJ exome

AF:

0.0834

Gnomad EAS exome

AF:

0.00397

Gnomad SAS exome

AF:

0.0358

Gnomad FIN exome

AF:

0.0437

Gnomad NFE exome

AF:

0.0616

Gnomad OTH exome

AF:

0.0510

GnomAD4 exome

AF:

0.0523

AC:

76397

AN:

1460794

Hom.:

2156

Cov.:

AF XY:

0.0525

AC XY:

38128

AN XY:

726730

show subpopulations

Gnomad4 AFR exome

AF:

0.0180

Gnomad4 AMR exome

AF:

0.0283

Gnomad4 ASJ exome

AF:

0.0824

Gnomad4 EAS exome

AF:

0.00189

Gnomad4 SAS exome

AF:

0.0353

Gnomad4 FIN exome

AF:

0.0462

Gnomad4 NFE exome

AF:

0.0571

Gnomad4 OTH exome

AF:

0.0501

GnomAD4 genome

AF:

0.0425

AC:

6477

AN:

152310

Hom.:

181

Cov.:

AF XY:

0.0413

AC XY:

3076

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0201

Gnomad4 AMR

AF:

0.0374

Gnomad4 ASJ

AF:

0.0848

Gnomad4 EAS

AF:

0.00656

Gnomad4 SAS

AF:

0.0333

Gnomad4 FIN

AF:

0.0446

Gnomad4 NFE

AF:

0.0583

Gnomad4 OTH

AF:

0.0483

Alfa

AF:

0.0524

Hom.:

Bravo

AF:

0.0413

Asia WGS

AF:

0.0300

AC:

105

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.9

DANN

Benign

0.33

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