rs2282991

Variant names:

• chr7-92715767-T-A
• rs2282991
• NM_001145306.2:c.537+9859A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-92715767-T-A
• chr7-92715767-T-C
• chr7-92715767-T-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.537+9859A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 152,274 control chromosomes in the GnomAD database, including 64,999 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 0.92 (64999 hom., cov: 32)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.537+9859A>T		intron_variant	Intron 4 of 7	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.537+9859A>T		intron_variant	Intron 4 of 7		NP_001250.1
CDK6	XM_047419716.1	c.537+9859A>T		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.537+9859A>T		intron_variant	Intron 4 of 7	1	NM_001145306.2	ENSP00000397087.3
CDK6	ENST00000265734.8	c.537+9859A>T		intron_variant	Intron 4 of 7	1		ENSP00000265734.4
CDK6	ENST00000473078.1	n.85+9859A>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140408 AN: 152156 Hom.: 64947 Cov.: 32

Gnomad AFR AF: 0.983

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.899

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.932

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

GnomAD4 genome AF: 0.923 AC: 140518 AN: 152274 Hom.: 64999 Cov.: 32 AF XY: 0.920 AC XY: 68478 AN XY: 74444

African (AFR) AF: 0.983 AC: 40858 AN: 41566

American (AMR) AF: 0.832 AC: 12714 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3397 AN: 3472

East Asian (EAS) AF: 0.927 AC: 4792 AN: 5172

South Asian (SAS) AF: 0.885 AC: 4264 AN: 4820

European-Finnish (FIN) AF: 0.899 AC: 9539 AN: 10612

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61801 AN: 68026

Other (OTH) AF: 0.933 AC: 1974 AN: 2116

Alfa AF: 0.912 Hom.: 7874

Bravo AF: 0.922

Asia WGS AF: 0.913 AC: 3178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.31
PhyloP100		0.59
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: rs2282991; hg19: chr7-92345081;