rs2285332

Positions:

• chr7-92612319-G-C

Variant summary

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

The NM_001145306.2(CDK6):​c.*2821C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 232,874 control chromosomes in the GnomAD database, including 14,470 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 0.33 (8946 hom., cov: 33)
  • Exomes 𝑓: 0.33 (5524 hom.)
• Consequence: CDK6 NM_001145306.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.*2821C>G		3_prime_UTR_variant	8/8	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.*2821C>G		3_prime_UTR_variant	8/8		NP_001250.1
CDK6	XM_047419716.1	c.*2821C>G		3_prime_UTR_variant	8/8		XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK6	ENST00000424848.3	c.*2821C>G		3_prime_UTR_variant	8/8	1	NM_001145306.2	ENSP00000397087	P1
CDK6	ENST00000265734.8	c.*2821C>G		3_prime_UTR_variant	8/8	1		ENSP00000265734	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49380 AN: 151990 Hom.: 8933 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.327 AC: 26384 AN: 80766 Hom.: 5524 Cov.: 0 AF XY: 0.322 AC XY: 11965 AN XY: 37112

Gnomad4 AFR exome AF: 0.388

Gnomad4 AMR exome AF: 0.448

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.717

Gnomad4 SAS exome AF: 0.284

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.325 AC: 49445 AN: 152108 Hom.: 8946 Cov.: 33 AF XY: 0.330 AC XY: 24521 AN XY: 74366

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.313

Alfa AF: 0.287 Hom.: 859

Bravo AF: 0.343

Asia WGS AF: 0.484 AC: 1680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.5
DANN	Benign	0.69

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: rs2285332; hg19: chr7-92241633;