rs2285332

Variant names:

• chr7-92612319-G-C
• rs2285332
• NM_001145306.2:c.*2821C>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.*2821C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 232,874 control chromosomes in the GnomAD database, including 14,470 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 0.33 (8946 hom., cov: 33)
  • Exomes 𝑓: 0.33 (5524 hom.)
• Consequence: CDK6 NM_001145306.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730
• Publications: 17 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.*2821C>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.*2821C>G		3_prime_UTR_variant	Exon 8 of 8		NP_001250.1
CDK6	XM_047419716.1	c.*2821C>G		3_prime_UTR_variant	Exon 8 of 8		XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK6	ENST00000424848.3	c.*2821C>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_001145306.2	ENSP00000397087.3
CDK6	ENST00000265734.8	c.*2821C>G		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000265734.4

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49380 AN: 151990 Hom.: 8933 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.327 AC: 26384 AN: 80766 Hom.: 5524 Cov.: 0 AF XY: 0.322 AC XY: 11965 AN XY: 37112

African (AFR) AF: 0.388 AC: 1508 AN: 3882

American (AMR) AF: 0.448 AC: 1115 AN: 2490

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 1240 AN: 5114

East Asian (EAS) AF: 0.717 AC: 8150 AN: 11366

South Asian (SAS) AF: 0.284 AC: 198 AN: 698

European-Finnish (FIN) AF: 0.190 AC: 11 AN: 58

Middle Eastern (MID) AF: 0.178 AC: 87 AN: 488

European-Non Finnish (NFE) AF: 0.244 AC: 12194 AN: 49918

Other (OTH) AF: 0.279 AC: 1881 AN: 6752

GnomAD4 genome AF: 0.325 AC: 49445 AN: 152108 Hom.: 8946 Cov.: 33 AF XY: 0.330 AC XY: 24521 AN XY: 74366

African (AFR) AF: 0.392 AC: 16259 AN: 41474

American (AMR) AF: 0.447 AC: 6837 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3468

East Asian (EAS) AF: 0.716 AC: 3697 AN: 5166

South Asian (SAS) AF: 0.299 AC: 1445 AN: 4828

European-Finnish (FIN) AF: 0.265 AC: 2812 AN: 10596

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16805 AN: 67976

Other (OTH) AF: 0.313 AC: 661 AN: 2110

Alfa AF: 0.287 Hom.: 859

Bravo AF: 0.343

Asia WGS AF: 0.484 AC: 1680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.5
DANN	Benign	0.69
PhyloP100		0.73
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: rs2285332; hg19: chr7-92241633;