Variant 7-92615108-C-T 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.*32G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,610,222 control chromosomes in the GnomAD database, including 41,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3194 hom., cov: 32)

Exomes 𝑓: 0.22 ( 38602 hom. )

Consequence

CDK6
NM_001145306.2 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.25

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 7-92615108-C-T is Benign according to our data. Variant chr7-92615108-C-T is described in ClinVar as [Benign]. Clinvar id is 1274922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
CDK6	NM_001145306.2 linkuse as main transcript	c.*32G>A	3_prime_UTR_variant	8/8	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8 linkuse as main transcript	c.*32G>A	3_prime_UTR_variant	8/8		NP_001250.1
CDK6	XM_047419716.1 linkuse as main transcript	c.*32G>A	3_prime_UTR_variant	8/8		XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
CDK6	ENST00000424848.3 linkuse as main transcript	c.*32G>A	3_prime_UTR_variant	8/8	1	NM_001145306.2	ENSP00000397087	P1
CDK6	ENST00000265734.8 linkuse as main transcript	c.*32G>A	3_prime_UTR_variant	8/8	1		ENSP00000265734	P1
CDK6	ENST00000467166.1 linkuse as main transcript	n.385G>A	non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

28707

AN:

151982

Hom.:

3198

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.0162

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.188

AC:

46719

AN:

248740

Hom.:

5172

AF XY:

0.190

AC XY:

25550

AN XY:

134490

show subpopulations

Gnomad AFR exome

AF:

0.0995

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.0137

Gnomad SAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.231

Gnomad NFE exome

AF:

0.249

Gnomad OTH exome

AF:

0.218

GnomAD4 exome

AF:

0.223

AC:

324622

AN:

1458122

Hom.:

38602

Cov.:

AF XY:

0.220

AC XY:

159420

AN XY:

725366

show subpopulations

Gnomad4 AFR exome

AF:

0.0940

Gnomad4 AMR exome

AF:

0.132

Gnomad4 ASJ exome

AF:

0.282

Gnomad4 EAS exome

AF:

0.0158

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.232

Gnomad4 NFE exome

AF:

0.244

Gnomad4 OTH exome

AF:

0.217

GnomAD4 genome

AF:

0.189

AC:

28710

AN:

152100

Hom.:

3194

Cov.:

AF XY:

0.186

AC XY:

13858

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.103

Gnomad4 AMR

AF:

0.168

Gnomad4 ASJ

AF:

0.285

Gnomad4 EAS

AF:

0.0163

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.223

Gnomad4 NFE

AF:

0.252

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.238

Hom.:

7424

Bravo

AF:

0.183

Asia WGS

AF:

0.0850

AC:

298

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

-0.89

CADD

Benign

1.7

DANN

Benign

0.51

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