7-92606850-T-C

Position:

• chr7-92606850-T-C

Variant summary

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

The NM_001145306.2(CDK6):​c.*8290A>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 0.833 in 232,752 control chromosomes in the GnomAD database, including 81,175 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 0.84 (53426 hom., cov: 32)
  • Exomes 𝑓: 0.83 (27749 hom.)
• Consequence: CDK6 NM_001145306.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.*8290A>G		3_prime_UTR_variant	8/8	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.*8290A>G		3_prime_UTR_variant	8/8		NP_001250.1
CDK6	XM_047419716.1	c.*8290A>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	c.*8290A>G		3_prime_UTR_variant	8/8	1	NM_001145306.2	ENSP00000397087.3
CDK6	ENST00000265734	c.*8290A>G		3_prime_UTR_variant	8/8	1		ENSP00000265734.4

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127070 AN: 152066 Hom.: 53379 Cov.: 32

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.823

GnomAD4 exome AF: 0.827 AC: 66653 AN: 80568 Hom.: 27749 Cov.: 0 AF XY: 0.826 AC XY: 30594 AN XY: 37022

Gnomad4 AFR exome AF: 0.887

Gnomad4 AMR exome AF: 0.865

Gnomad4 ASJ exome AF: 0.794

Gnomad4 EAS exome AF: 0.978

Gnomad4 SAS exome AF: 0.918

Gnomad4 FIN exome AF: 0.767

Gnomad4 NFE exome AF: 0.791

Gnomad4 OTH exome AF: 0.812

GnomAD4 genome AF: 0.836 AC: 127176 AN: 152184 Hom.: 53426 Cov.: 32 AF XY: 0.838 AC XY: 62344 AN XY: 74416

Gnomad4 AFR AF: 0.893

Gnomad4 AMR AF: 0.867

Gnomad4 ASJ AF: 0.793

Gnomad4 EAS AF: 0.982

Gnomad4 SAS AF: 0.922

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.824

Alfa AF: 0.798 Hom.: 66613

Bravo AF: 0.841

Asia WGS AF: 0.927 AC: 3219 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.5
DANN	Benign	0.60

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: rs8179; hg19: chr7-92236164;