rs2374589

chr7-92816166-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145306.2(CDK6):c.233+16925T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,190 control chromosomes in the GnomAD database, including 2,336 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 0.14 (2336 hom., cov: 32)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK6	NM_001145306.2	c.233+16925T>C		intron_variant		ENST00000424848.3
CDK6	NM_001259.8	c.233+16925T>C		intron_variant
CDK6	XM_047419716.1	c.233+16925T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK6	ENST00000424848.3	c.233+16925T>C		intron_variant		1	NM_001145306.2	P1
CDK6	ENST00000265734.8	c.233+16925T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20829 AN: 152072 Hom.: 2316 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.0814

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.137 AC: 20896 AN: 152190 Hom.: 2336 Cov.: 32 AF XY: 0.138 AC XY: 10294 AN XY: 74432

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.0885

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.0820

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.0442

Gnomad4 NFE AF: 0.0668

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0928 Hom.: 514

Bravo AF: 0.142

Asia WGS AF: 0.234 AC: 814 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	2.5
Dann	Benign	0.48
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

Other links and lift over

dbSNP: rs2374589; hg19: chr7-92445480;