rs10

Variant names:

• chr7-92754574-A-C
• rs10
• NM_001145306.2:c.369+20122T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-92754574-A-C
• chr7-92754574-A-G
• chr7-92754574-A-T

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+20122T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.96 in 152,306 control chromosomes in the GnomAD database, including 70,143 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 0.96 (70143 hom., cov: 32)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• Publications: 1 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.369+20122T>G		intron_variant	Intron 3 of 7	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.369+20122T>G		intron_variant	Intron 3 of 7		NP_001250.1
CDK6	XM_047419716.1	c.369+20122T>G		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+20122T>G		intron_variant	Intron 3 of 7	1	NM_001145306.2	ENSP00000397087.3
CDK6	ENST00000265734.8	c.369+20122T>G		intron_variant	Intron 3 of 7	1		ENSP00000265734.4

Frequencies

GnomAD3 genomes AF: 0.959 AC: 146019 AN: 152188 Hom.: 70082 Cov.: 32

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.989

Gnomad FIN AF: 0.928

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.973

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

GnomAD4 genome AF: 0.960 AC: 146139 AN: 152306 Hom.: 70143 Cov.: 32 AF XY: 0.960 AC XY: 71459 AN XY: 74456

African (AFR) AF: 0.990 AC: 41174 AN: 41574

American (AMR) AF: 0.961 AC: 14704 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.983 AC: 3414 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5185 AN: 5186

South Asian (SAS) AF: 0.989 AC: 4775 AN: 4826

European-Finnish (FIN) AF: 0.928 AC: 9827 AN: 10584

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.938 AC: 63802 AN: 68038

Other (OTH) AF: 0.974 AC: 2060 AN: 2116

Alfa AF: 0.936 Hom.: 12988

Bravo AF: 0.964

Asia WGS AF: 0.995 AC: 3458 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.15
DANN	Benign	0.80
PhyloP100		-0.56
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: rs10; hg19: chr7-92383888;