rs3802073

Variant names:

• chr7-92773166-C-T
• rs3802073
• NM_001145306.2:c.369+1530G>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.369+1530G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,070 control chromosomes in the GnomAD database, including 2,636 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 0.16 (2636 hom., cov: 32)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.369+1530G>A		intron_variant	Intron 3 of 7	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.369+1530G>A		intron_variant	Intron 3 of 7		NP_001250.1
CDK6	XM_047419716.1	c.369+1530G>A		intron_variant	Intron 3 of 7		XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK6	ENST00000424848.3	c.369+1530G>A		intron_variant	Intron 3 of 7	1	NM_001145306.2	ENSP00000397087.3
CDK6	ENST00000265734.8	c.369+1530G>A		intron_variant	Intron 3 of 7	1		ENSP00000265734.4

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24760 AN: 151952 Hom.: 2619 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.163 AC: 24819 AN: 152070 Hom.: 2636 Cov.: 32 AF XY: 0.168 AC XY: 12496 AN XY: 74334

African (AFR) AF: 0.287 AC: 11917 AN: 41470

American (AMR) AF: 0.102 AC: 1564 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0740 AC: 257 AN: 3472

East Asian (EAS) AF: 0.154 AC: 795 AN: 5170

South Asian (SAS) AF: 0.294 AC: 1415 AN: 4820

European-Finnish (FIN) AF: 0.162 AC: 1713 AN: 10552

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0997 AC: 6776 AN: 67994

Other (OTH) AF: 0.149 AC: 314 AN: 2106

Alfa AF: 0.114 Hom.: 1384

Bravo AF: 0.158

Asia WGS AF: 0.289 AC: 1003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.21
PhyloP100		-0.24
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: rs3802073; hg19: chr7-92402480;