7-92606850-T-C

Variant names:

• chr7-92606850-T-C
• rs8179
• NM_001145306.2:c.*8290A>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.*8290A>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 0.833 in 232,752 control chromosomes in the GnomAD database, including 81,175 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 0.84 (53426 hom., cov: 32)
  • Exomes 𝑓: 0.83 (27749 hom.)
• Consequence: CDK6 NM_001145306.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312
• Publications: 32 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK6	NM_001145306.2	MANE Select	c.*8290A>G		3_prime_UTR	Exon 8 of 8	NP_001138778.1
	CDK6	NM_001259.8		c.*8290A>G		3_prime_UTR	Exon 8 of 8	NP_001250.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK6	ENST00000424848.3	TSL:1 MANE Select	c.*8290A>G		3_prime_UTR	Exon 8 of 8	ENSP00000397087.3
	CDK6	ENST00000265734.8	TSL:1	c.*8290A>G		3_prime_UTR	Exon 8 of 8	ENSP00000265734.4

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127070 AN: 152066 Hom.: 53379 Cov.: 32

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.823

GnomAD4 exome AF: 0.827 AC: 66653 AN: 80568 Hom.: 27749 Cov.: 0 AF XY: 0.826 AC XY: 30594 AN XY: 37022

African (AFR) AF: 0.887 AC: 3445 AN: 3884

American (AMR) AF: 0.865 AC: 2146 AN: 2482

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 4046 AN: 5098

East Asian (EAS) AF: 0.978 AC: 11047 AN: 11298

South Asian (SAS) AF: 0.918 AC: 641 AN: 698

European-Finnish (FIN) AF: 0.767 AC: 46 AN: 60

Middle Eastern (MID) AF: 0.814 AC: 397 AN: 488

European-Non Finnish (NFE) AF: 0.791 AC: 39414 AN: 49824

Other (OTH) AF: 0.812 AC: 5471 AN: 6736

GnomAD4 genome AF: 0.836 AC: 127176 AN: 152184 Hom.: 53426 Cov.: 32 AF XY: 0.838 AC XY: 62344 AN XY: 74416

African (AFR) AF: 0.893 AC: 37070 AN: 41524

American (AMR) AF: 0.867 AC: 13264 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2753 AN: 3470

East Asian (EAS) AF: 0.982 AC: 5089 AN: 5184

South Asian (SAS) AF: 0.922 AC: 4446 AN: 4822

European-Finnish (FIN) AF: 0.792 AC: 8382 AN: 10580

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53525 AN: 67984

Other (OTH) AF: 0.824 AC: 1741 AN: 2112

Alfa AF: 0.806 Hom.: 166021

Bravo AF: 0.841

Asia WGS AF: 0.927 AC: 3219 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.5
DANN	Benign	0.60
PhyloP100		0.31
Mutation Taster		=99/1	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: rs8179; hg19: chr7-92236164;