rs2282987

Variant names:

• chr7-92683489-G-C
• rs2282987
• NM_001145306.2:c.538-11954C>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.538-11954C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 152,244 control chromosomes in the GnomAD database, including 417 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 0.040 (417 hom., cov: 32)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.538-11954C>G		intron_variant	Intron 4 of 7	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.538-11954C>G		intron_variant	Intron 4 of 7		NP_001250.1
CDK6	XM_047419716.1	c.538-11954C>G		intron_variant	Intron 4 of 7		XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK6	ENST00000424848.3	c.538-11954C>G		intron_variant	Intron 4 of 7	1	NM_001145306.2	ENSP00000397087.3
CDK6	ENST00000265734.8	c.538-11954C>G		intron_variant	Intron 4 of 7	1		ENSP00000265734.4
CDK6	ENST00000473078.1	n.86-11954C>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 6023 AN: 152126 Hom.: 414 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0398

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.00972

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00256

Gnomad OTH AF: 0.0450

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

GnomAD4 genome AF: 0.0397 AC: 6049 AN: 152244 Hom.: 417 Cov.: 32 AF XY: 0.0413 AC XY: 3076 AN XY: 74416

African (AFR) AF: 0.0767 AC: 3185 AN: 41534

American (AMR) AF: 0.0400 AC: 612 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

East Asian (EAS) AF: 0.327 AC: 1692 AN: 5172

South Asian (SAS) AF: 0.0320 AC: 154 AN: 4820

European-Finnish (FIN) AF: 0.00972 AC: 103 AN: 10600

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00256 AC: 174 AN: 68034

Other (OTH) AF: 0.0445 AC: 94 AN: 2112

Alfa AF: 0.0219 Hom.: 16

Bravo AF: 0.0460

Asia WGS AF: 0.163 AC: 564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.2
DANN	Benign	0.62
PhyloP100		2.1
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: rs2282987; hg19: chr7-92312803;