rs10

chr7-92754574-A-Cchr7-92754574-A-Gchr7-92754574-A-T

Variant summary

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

The NM_001145306.2(CDK6):c.369+20122T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.96 in 152,306 control chromosomes in the GnomAD database, including 70,143 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 0.96 (70143 hom., cov: 32)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564

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 (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK6	NM_001145306.2	c.369+20122T>G		intron_variant		ENST00000424848.3
CDK6	NM_001259.8	c.369+20122T>G		intron_variant
CDK6	XM_047419716.1	c.369+20122T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK6	ENST00000424848.3	c.369+20122T>G		intron_variant		1	NM_001145306.2	P1
CDK6	ENST00000265734.8	c.369+20122T>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.959 AC: 146019 AN: 152188 Hom.: 70082 Cov.: 32

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.989

Gnomad FIN AF: 0.928

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.973

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

GnomAD4 genome AF: 0.960 AC: 146139 AN: 152306 Hom.: 70143 Cov.: 32 AF XY: 0.960 AC XY: 71459 AN XY: 74456

Gnomad4 AFR AF: 0.990

Gnomad4 AMR AF: 0.961

Gnomad4 ASJ AF: 0.983

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.989

Gnomad4 FIN AF: 0.928

Gnomad4 NFE AF: 0.938

Gnomad4 OTH AF: 0.974

Alfa AF: 0.925 Hom.: 3661

Bravo AF: 0.964

Asia WGS AF: 0.995 AC: 3458 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.15
Dann	Benign	0.80

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: rs10; hg19: chr7-92383888;