dbSNP rs42235: CDK6:c.699-555G>A (chr7-92618762-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001145306.2(CDK6):c.699-555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,066 control chromosomes in the GnomAD database, including 7,817 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 7817 hom., cov: 32)

Consequence

CDK6
NM_001145306.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.660

Publications

53 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive primary microcephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
microcephaly 12, primary, autosomal recessive
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CDK6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CDK6	NM_001145306.2 link	c.699-555G>A	intron_variant	Intron 6 of 7	ENST00000424848.3	NP_001138778.1	Q00534
CDK6	NM_001259.8 link	c.699-555G>A	intron_variant	Intron 6 of 7		NP_001250.1	Q00534
CDK6	XM_047419716.1 link	c.699-555G>A	intron_variant	Intron 6 of 7		XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK6	ENST00000424848.3 link	c.699-555G>A		intron_variant	Intron 6 of 7	1	NM_001145306.2	ENSP00000397087.3		Q00534
CDK6	ENST00000265734.8 link	c.699-555G>A		intron_variant	Intron 6 of 7	1		ENSP00000265734.4		Q00534

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46999

AN:

151948

Hom.:

7809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.350

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.0260

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.312

Gnomad OTH

AF:

0.305

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.309

AC:

47050

AN:

152066

Hom.:

7817

Cov.:

AF XY:

0.304

AC XY:

22593

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.393

AC:

16287

AN:

41458

American (AMR)

AF:

0.228

AC:

3481

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

1293

AN:

3470

East Asian (EAS)

AF:

0.0260

AC:

135

AN:

5186

South Asian (SAS)

AF:

0.151

AC:

727

AN:

4824

European-Finnish (FIN)

AF:

0.270

AC:

2853

AN:

10556

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.312

AC:

21217

AN:

67970

Other (OTH)

AF:

0.303

AC:

639

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1639

3278

4917

6556

8195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.305

Hom.:

24249

Bravo

AF:

0.311

Asia WGS

AF:

0.133

AC:

465

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.36

(source)

DANN

Benign

0.33

PhyloP100

-0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over