7-92614405-C-T

Position:

• chr7-92614405-C-T

Variant summary

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

The NM_001145306.2(CDK6):​c.*735G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 232,660 control chromosomes in the GnomAD database, including 10,883 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 0.30 (7464 hom., cov: 32)
  • Exomes 𝑓: 0.27 (3419 hom.)
• Consequence: CDK6 NM_001145306.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.*735G>A		3_prime_UTR_variant	8/8	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.*735G>A		3_prime_UTR_variant	8/8		NP_001250.1
CDK6	XM_047419716.1	c.*735G>A		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.*735G>A		3_prime_UTR_variant	8/8	1	NM_001145306.2	ENSP00000397087.3
CDK6	ENST00000265734	c.*735G>A		3_prime_UTR_variant	8/8	1		ENSP00000265734.4

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45954 AN: 151842 Hom.: 7456 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.269 AC: 21695 AN: 80700 Hom.: 3419 Cov.: 0 AF XY: 0.271 AC XY: 10030 AN XY: 37066

Gnomad4 AFR exome AF: 0.381

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.372

Gnomad4 EAS exome AF: 0.0162

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.303 AC: 46004 AN: 151960 Hom.: 7464 Cov.: 32 AF XY: 0.297 AC XY: 22094 AN XY: 74272

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.0211

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.300

Alfa AF: 0.313 Hom.: 2677

Bravo AF: 0.305

Asia WGS AF: 0.130 AC: 454 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.63

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: rs42038; hg19: chr7-92243719;