rs2282979

chr7-92635679-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.648-12593A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,154 control chromosomes in the GnomAD database, including 4,793 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 0.24 (4793 hom., cov: 32)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK6	NM_001145306.2	c.648-12593A>G		intron_variant		ENST00000424848.3
CDK6	NM_001259.8	c.648-12593A>G		intron_variant
CDK6	XM_047419716.1	c.648-12593A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK6	ENST00000424848.3	c.648-12593A>G		intron_variant		1	NM_001145306.2	P1
CDK6	ENST00000265734.8	c.648-12593A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36445 AN: 152036 Hom.: 4799 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.240 AC: 36449 AN: 152154 Hom.: 4793 Cov.: 32 AF XY: 0.239 AC XY: 17807 AN XY: 74370

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.276

Alfa AF: 0.279 Hom.: 12203

Bravo AF: 0.246

Asia WGS AF: 0.151 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.6
Dann	Benign	0.65

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: rs2282979; hg19: chr7-92264993;