rs2282983

Variant names:

• chr7-92650049-T-C
• rs2282983
• NM_001145306.2:c.647+21377A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145306.2(CDK6):​c.647+21377A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,048 control chromosomes in the GnomAD database, including 14,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.43 (14933 hom., cov: 32)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -1.03
• Publications: 10 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)

LOC112268009 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.647+21377A>G		intron_variant	Intron 5 of 7	ENST00000424848.3	NP_001138778.1
LOC112268009	XR_002956577.2	n.12622A>G		non_coding_transcript_exon_variant	Exon 1 of 2
CDK6	NM_001259.8	c.647+21377A>G		intron_variant	Intron 5 of 7		NP_001250.1
CDK6	XM_047419716.1	c.647+21377A>G		intron_variant	Intron 5 of 7		XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK6	ENST00000424848.3	c.647+21377A>G		intron_variant	Intron 5 of 7	1	NM_001145306.2	ENSP00000397087.3
CDK6	ENST00000265734.8	c.647+21377A>G		intron_variant	Intron 5 of 7	1		ENSP00000265734.4
ENSG00000286742	ENST00000668236.1	n.113+2031T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65731 AN: 151932 Hom.: 14909 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.433 AC: 65815 AN: 152048 Hom.: 14933 Cov.: 32 AF XY: 0.436 AC XY: 32360 AN XY: 74300

African (AFR) AF: 0.578 AC: 23970 AN: 41470

American (AMR) AF: 0.436 AC: 6664 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1612 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1415 AN: 5172

South Asian (SAS) AF: 0.385 AC: 1857 AN: 4824

European-Finnish (FIN) AF: 0.381 AC: 4027 AN: 10560

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24862 AN: 67958

Other (OTH) AF: 0.437 AC: 922 AN: 2112

Alfa AF: 0.394 Hom.: 34643

Bravo AF: 0.443

Asia WGS AF: 0.404 AC: 1405 AN: 3476

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Behcet disease Other:1

Nov 14, 2021

Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2282983; hg19: chr7-92279363;