7-92618225-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001145306.2(CDK6):c.699-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 1,613,104 control chromosomes in the GnomAD database, including 2,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (181 hom., cov: 32)
  • Exomes 𝑓: 0.052 (2156 hom.)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0160

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-92618225-A-G is Benign according to our data. Variant chr7-92618225-A-G is described in ClinVar as [Benign]. Clinvar id is 1226582.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK6	NM_001145306.2	c.699-18T>C		intron_variant		ENST00000424848.3
CDK6	NM_001259.8	c.699-18T>C		intron_variant
CDK6	XM_047419716.1	c.699-18T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK6	ENST00000424848.3	c.699-18T>C		intron_variant		1	NM_001145306.2	P1
CDK6	ENST00000265734.8	c.699-18T>C		intron_variant		1		P1
CDK6	ENST00000467166.1	n.53T>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.0425 AC: 6471 AN: 152192 Hom.: 182 Cov.: 32

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.0848

Gnomad EAS AF: 0.00655

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0583

Gnomad OTH AF: 0.0483

GnomAD3 exomes AF: 0.0458 AC: 11479 AN: 250714 Hom.: 325 AF XY: 0.0470 AC XY: 6374 AN XY: 135494

Gnomad AFR exome AF: 0.0197

Gnomad AMR exome AF: 0.0266

Gnomad ASJ exome AF: 0.0834

Gnomad EAS exome AF: 0.00397

Gnomad SAS exome AF: 0.0358

Gnomad FIN exome AF: 0.0437

Gnomad NFE exome AF: 0.0616

Gnomad OTH exome AF: 0.0510

GnomAD4 exome AF: 0.0523 AC: 76397 AN: 1460794 Hom.: 2156 Cov.: 31 AF XY: 0.0525 AC XY: 38128 AN XY: 726730

Gnomad4 AFR exome AF: 0.0180

Gnomad4 AMR exome AF: 0.0283

Gnomad4 ASJ exome AF: 0.0824

Gnomad4 EAS exome AF: 0.00189

Gnomad4 SAS exome AF: 0.0353

Gnomad4 FIN exome AF: 0.0462

Gnomad4 NFE exome AF: 0.0571

Gnomad4 OTH exome AF: 0.0501

GnomAD4 genome AF: 0.0425 AC: 6477 AN: 152310 Hom.: 181 Cov.: 32 AF XY: 0.0413 AC XY: 3076 AN XY: 74464

Gnomad4 AFR AF: 0.0201

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.0848

Gnomad4 EAS AF: 0.00656

Gnomad4 SAS AF: 0.0333

Gnomad4 FIN AF: 0.0446

Gnomad4 NFE AF: 0.0583

Gnomad4 OTH AF: 0.0483

Alfa AF: 0.0524 Hom.: 78

Bravo AF: 0.0413

Asia WGS AF: 0.0300 AC: 105 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	-0.92
Cadd	Benign	3.9
Dann	Benign	0.33
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: rs3731373; hg19: chr7-92247539; COSMIC: COSV99720907;