chr7-92618019-A-G

Position:

• chr7-92618019-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145306.2(CDK6):​c.834+53T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,589,610 control chromosomes in the GnomAD database, including 44,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3823 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40514 hom.)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.406

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 7-92618019-A-G is Benign according to our data. Variant chr7-92618019-A-G is described in ClinVar as [Benign]. Clinvar id is 1233941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK6	NM_001145306.2	c.834+53T>C		intron_variant		ENST00000424848.3
CDK6	NM_001259.8	c.834+53T>C		intron_variant
CDK6	XM_047419716.1	c.834+53T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK6	ENST00000424848.3	c.834+53T>C		intron_variant		1	NM_001145306.2	P1
CDK6	ENST00000265734.8	c.834+53T>C		intron_variant		1		P1
CDK6	ENST00000467166.1	n.206+53T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32890 AN: 152124 Hom.: 3825 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.233 AC: 335169 AN: 1437368 Hom.: 40514 AF XY: 0.230 AC XY: 163862 AN XY: 713436

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.247

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.216 AC: 32900 AN: 152242 Hom.: 3823 Cov.: 32 AF XY: 0.215 AC XY: 15979 AN XY: 74422

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.235

Alfa AF: 0.236 Hom.: 814

Bravo AF: 0.216

Asia WGS AF: 0.142 AC: 496 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.94
CADD	Benign	1.7
DANN	Benign	0.74

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: rs42043; hg19: chr7-92247333;