Variant chr7-92671484-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_001145306.2(CDK6):c.589G>T(p.Ala197Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CDK6
NM_001145306.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.90

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CDK6. . Gene score misZ 3.0596 (greater than the threshold 3.09). Trascript score misZ 3.1324 (greater than threshold 3.09). GenCC has associacion of gene with autosomal recessive primary microcephaly, microcephaly 12, primary, autosomal recessive.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CDK6	NM_001145306.2 linkuse as main transcript	c.589G>T	p.Ala197Ser	missense_variant	5/8	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8 linkuse as main transcript	c.589G>T	p.Ala197Ser	missense_variant	5/8		NP_001250.1
CDK6	XM_047419716.1 linkuse as main transcript	c.589G>T	p.Ala197Ser	missense_variant	5/8		XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CDK6	ENST00000424848.3 linkuse as main transcript	c.589G>T	p.Ala197Ser	missense_variant	5/8	1	NM_001145306.2	ENSP00000397087	P1
CDK6	ENST00000265734.8 linkuse as main transcript	c.589G>T	p.Ala197Ser	missense_variant	5/8	1		ENSP00000265734	P1
CDK6	ENST00000473078.1 linkuse as main transcript	n.137G>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1429148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710998

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.00051

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;T

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

.;D

M_CAP

Uncertain

0.21

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-0.54

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.7

N;N

REVEL

Uncertain

0.43

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

1.0

D;D

Vest4

0.59

MutPred

0.53

Gain of glycosylation at A197 (P = 0.0477);Gain of glycosylation at A197 (P = 0.0477);

MVP

0.69

MPC

1.1

ClinPred

0.97

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.75

gMVP

0.61

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over