7-92609830-A-G

Variant names:

• chr7-92609830-A-G
• rs42034
• NM_001145306.2:c.*5310T>C

Variant summary

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

The NM_001145306.2(CDK6):​c.*5310T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 230,198 control chromosomes in the GnomAD database, including 5,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.19 (3303 hom., cov: 32)
  • Exomes 𝑓: 0.22 (2088 hom.)
• Consequence: CDK6 NM_001145306.2 3_prime_UTR
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.370
• Publications: 18 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.*5310T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.*5310T>C		3_prime_UTR_variant	Exon 8 of 8		NP_001250.1
CDK6	XM_047419716.1	c.*5310T>C		3_prime_UTR_variant	Exon 8 of 8		XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK6	ENST00000424848.3	c.*5310T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_001145306.2	ENSP00000397087.3
CDK6	ENST00000265734.8	c.*5310T>C		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000265734.4

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29268 AN: 152026 Hom.: 3308 Cov.: 32

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.221 AC: 17277 AN: 78054 Hom.: 2088 Cov.: 0 AF XY: 0.222 AC XY: 7978 AN XY: 35932

African (AFR) AF: 0.0831 AC: 312 AN: 3754

American (AMR) AF: 0.237 AC: 569 AN: 2400

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1445 AN: 4972

East Asian (EAS) AF: 0.111 AC: 1214 AN: 10906

South Asian (SAS) AF: 0.112 AC: 76 AN: 676

European-Finnish (FIN) AF: 0.293 AC: 17 AN: 58

Middle Eastern (MID) AF: 0.245 AC: 116 AN: 474

European-Non Finnish (NFE) AF: 0.248 AC: 11990 AN: 48254

Other (OTH) AF: 0.234 AC: 1538 AN: 6560

GnomAD4 genome AF: 0.192 AC: 29261 AN: 152144 Hom.: 3303 Cov.: 32 AF XY: 0.192 AC XY: 14253 AN XY: 74366

African (AFR) AF: 0.0832 AC: 3455 AN: 41542

American (AMR) AF: 0.215 AC: 3288 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3466

East Asian (EAS) AF: 0.103 AC: 533 AN: 5178

South Asian (SAS) AF: 0.111 AC: 536 AN: 4816

European-Finnish (FIN) AF: 0.229 AC: 2423 AN: 10566

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17153 AN: 67968

Other (OTH) AF: 0.224 AC: 473 AN: 2114

Alfa AF: 0.222 Hom.: 7309

Bravo AF: 0.190

Asia WGS AF: 0.133 AC: 462 AN: 3474

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Behcet disease Other:1

Nov 14, 2021

Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.66
PhyloP100		0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs42034; hg19: chr7-92239144;