rs2079147

Variant names:

• chr7-92703061-A-G
• rs2079147
• NM_001145306.2:c.537+22565T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145306.2(CDK6):​c.537+22565T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,052 control chromosomes in the GnomAD database, including 13,209 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 0.38 (13209 hom., cov: 31)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450
• Publications: 18 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.537+22565T>C		intron_variant	Intron 4 of 7	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.537+22565T>C		intron_variant	Intron 4 of 7		NP_001250.1
CDK6	XM_047419716.1	c.537+22565T>C		intron_variant	Intron 4 of 7		XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK6	ENST00000424848.3	c.537+22565T>C		intron_variant	Intron 4 of 7	1	NM_001145306.2	ENSP00000397087.3
CDK6	ENST00000265734.8	c.537+22565T>C		intron_variant	Intron 4 of 7	1		ENSP00000265734.4
CDK6	ENST00000473078.1	n.85+22565T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57217 AN: 151934 Hom.: 13202 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.376 AC: 57228 AN: 152052 Hom.: 13209 Cov.: 31 AF XY: 0.373 AC XY: 27700 AN XY: 74324

African (AFR) AF: 0.119 AC: 4921 AN: 41510

American (AMR) AF: 0.422 AC: 6439 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1631 AN: 3468

East Asian (EAS) AF: 0.127 AC: 655 AN: 5174

South Asian (SAS) AF: 0.357 AC: 1723 AN: 4822

European-Finnish (FIN) AF: 0.500 AC: 5271 AN: 10548

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35048 AN: 67954

Other (OTH) AF: 0.394 AC: 829 AN: 2104

Alfa AF: 0.451 Hom.: 33031

Bravo AF: 0.360

Asia WGS AF: 0.210 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.93
DANN	Benign	0.37
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2079147; hg19: chr7-92332375;