7-92617798-C-T

Variant names:

• chr7-92617798-C-T
• rs42042
• NM_001145306.2:c.834+274G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

CDK6 Gene-Disease associations (from GenCC):

• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• microcephaly 12, primary, autosomal recessive

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145306.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK6	NM_001145306.2	MANE Select	c.834+274G>A		intron	N/A	NP_001138778.1	Q00534
	CDK6	NM_001259.8		c.834+274G>A		intron	N/A	NP_001250.1	Q00534

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK6	ENST00000424848.3	TSL:1 MANE Select	c.834+274G>A		intron	N/A	ENSP00000397087.3	Q00534
	CDK6	ENST00000265734.8	TSL:1	c.834+274G>A		intron	N/A	ENSP00000265734.4	Q00534
	CDK6	ENST00000906280.1		c.834+274G>A		intron	N/A	ENSP00000576339.1

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

African (AFR) AF: 0.756 AC: 31368 AN: 41512

American (AMR) AF: 0.690 AC: 10546 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1778 AN: 3468

East Asian (EAS) AF: 0.807 AC: 4172 AN: 5172

South Asian (SAS) AF: 0.404 AC: 1946 AN: 4822

European-Finnish (FIN) AF: 0.498 AC: 5270 AN: 10580

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34394 AN: 67968

Other (OTH) AF: 0.587 AC: 1235 AN: 2104

Alfa AF: 0.572 Hom.: 11826

Bravo AF: 0.625

Asia WGS AF: 0.632 AC: 2196 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.48
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs42042; hg19: chr7-92247112;