7-92622889-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001145306.2(CDK6):c.698+147G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 593,384 control chromosomes in the GnomAD database, including 17,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3930 hom., cov: 31)
  • Exomes 𝑓: 0.23 (13599 hom.)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.68

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=-0.25).
• BP6: Variant 7-92622889-C-G is Benign according to our data. Variant chr7-92622889-C-G is described in ClinVar as [Benign]. Clinvar id is 1250250.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK6	NM_001145306.2	c.698+147G>C		intron_variant		ENST00000424848.3
CDK6	NM_001259.8	c.698+147G>C		intron_variant
CDK6	XM_047419716.1	c.698+147G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK6	ENST00000424848.3	c.698+147G>C		intron_variant		1	NM_001145306.2	P1
CDK6	ENST00000265734.8	c.698+147G>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31304 AN: 151726 Hom.: 3938 Cov.: 31

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.0227

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.233 AC: 103030 AN: 441540 Hom.: 13599 AF XY: 0.230 AC XY: 53396 AN XY: 232374

Gnomad4 AFR exome AF: 0.0823

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.0236

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.206 AC: 31292 AN: 151844 Hom.: 3930 Cov.: 31 AF XY: 0.204 AC XY: 15135 AN XY: 74162

Gnomad4 AFR AF: 0.0821

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.0228

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.251

Alfa AF: 0.147 Hom.: 306

Bravo AF: 0.201

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
Cadd	Benign	20
Dann	Benign	0.81
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: rs42046; hg19: chr7-92252203; COSMIC: COSV56014940; COSMIC: COSV56014940;