7-92697154-C-T

Variant names:

• chr7-92697154-C-T
• rs2282990
• NM_001145306.2:c.538-25619G>A

Variant summary

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

The NM_001145306.2(CDK6):​c.538-25619G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 152,236 control chromosomes in the GnomAD database, including 821 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 0.097 (821 hom., cov: 32)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• Publications: 7 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=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.538-25619G>A		intron_variant	Intron 4 of 7	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.538-25619G>A		intron_variant	Intron 4 of 7		NP_001250.1
CDK6	XM_047419716.1	c.538-25619G>A		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.538-25619G>A		intron_variant	Intron 4 of 7	1	NM_001145306.2	ENSP00000397087.3
CDK6	ENST00000265734.8	c.538-25619G>A		intron_variant	Intron 4 of 7	1		ENSP00000265734.4
CDK6	ENST00000473078.1	n.86-25619G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14745 AN: 152118 Hom.: 821 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.0903

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

GnomAD4 genome AF: 0.0969 AC: 14759 AN: 152236 Hom.: 821 Cov.: 32 AF XY: 0.102 AC XY: 7566 AN XY: 74440

African (AFR) AF: 0.104 AC: 4333 AN: 41532

American (AMR) AF: 0.0665 AC: 1018 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3470

East Asian (EAS) AF: 0.137 AC: 710 AN: 5174

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4826

European-Finnish (FIN) AF: 0.128 AC: 1358 AN: 10596

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0810 AC: 5509 AN: 68016

Other (OTH) AF: 0.0951 AC: 201 AN: 2114

Alfa AF: 0.0829 Hom.: 886

Bravo AF: 0.0898

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.80
PhyloP100		0.52
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: rs2282990; hg19: chr7-92326468;