7-92617798-C-T

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.834+274G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,118 control chromosomes in the GnomAD database, including 28,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.60 (28519 hom., cov: 33)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.82

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=-0.91).
• BP6: Variant 7-92617798-C-T is Benign according to our data. Variant chr7-92617798-C-T is described in ClinVar as [Benign]. Clinvar id is 1232569.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK6	NM_001145306.2	c.834+274G>A		intron_variant		ENST00000424848.3
CDK6	NM_001259.8	c.834+274G>A		intron_variant
CDK6	XM_047419716.1	c.834+274G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK6	ENST00000424848.3	c.834+274G>A		intron_variant		1	NM_001145306.2	P1
CDK6	ENST00000265734.8	c.834+274G>A		intron_variant		1		P1
CDK6	ENST00000467166.1	n.206+274G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91145 AN: 152002 Hom.: 28467 Cov.: 33

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.600 AC: 91261 AN: 152118 Hom.: 28519 Cov.: 33 AF XY: 0.602 AC XY: 44733 AN XY: 74366

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.587

Alfa AF: 0.559 Hom.: 6490

Bravo AF: 0.625

Asia WGS AF: 0.632 AC: 2196 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.24
Dann	Benign	0.48

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: rs42042; hg19: chr7-92247112;