Variant 7-92622889-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001145306.2(CDK6):c.698+147G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 593,384 control chromosomes in the GnomAD database, including 17,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3930 hom., cov: 31)

Exomes 𝑓: 0.23 ( 13599 hom. )

Consequence

CDK6
NM_001145306.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.68

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 7-92622889-C-G is Benign according to our data. Variant chr7-92622889-C-G is described in ClinVar as [Benign]. Clinvar id is 1250250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CDK6	NM_001145306.2 linkuse as main transcript	c.698+147G>C	intron_variant	ENST00000424848.3
CDK6	NM_001259.8 linkuse as main transcript	c.698+147G>C	intron_variant
CDK6	XM_047419716.1 linkuse as main transcript	c.698+147G>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK6	ENST00000424848.3 linkuse as main transcript	c.698+147G>C		intron_variant		1	NM_001145306.2	P1
CDK6	ENST00000265734.8 linkuse as main transcript	c.698+147G>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31304

AN:

151726

Hom.:

3938

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0822

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.0227

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.254

GnomAD4 exome

AF:

0.233

AC:

103030

AN:

441540

Hom.:

13599

AF XY:

0.230

AC XY:

53396

AN XY:

232374

show subpopulations

Gnomad4 AFR exome

AF:

0.0823

Gnomad4 AMR exome

AF:

0.182

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.0236

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.273

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.206

AC:

31292

AN:

151844

Hom.:

3930

Cov.:

AF XY:

0.204

AC XY:

15135

AN XY:

74162

show subpopulations

Gnomad4 AFR

AF:

0.0821

Gnomad4 AMR

AF:

0.209

Gnomad4 ASJ

AF:

0.345

Gnomad4 EAS

AF:

0.0228

Gnomad4 SAS

AF:

0.137

Gnomad4 FIN

AF:

0.247

Gnomad4 NFE

AF:

0.283

Gnomad4 OTH

AF:

0.251

Alfa

AF:

0.147

Hom.:

306

Bravo

AF:

0.201

Asia WGS

AF:

0.0930

AC:

324

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

-0.25

CADD

Benign

DANN

Benign

0.81

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