7-92671273-G-A

Position:

• chr7-92671273-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145306.2(CDK6):​c.647+153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 455,712 control chromosomes in the GnomAD database, including 6,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3629 hom., cov: 32)
  • Exomes 𝑓: 0.11 (2434 hom.)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.42

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 7-92671273-G-A is Benign according to our data. Variant chr7-92671273-G-A is described in ClinVar as [Benign]. Clinvar id is 1242376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.647+153C>T		intron_variant		ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.647+153C>T		intron_variant			NP_001250.1
CDK6	XM_047419716.1	c.647+153C>T		intron_variant			XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK6	ENST00000424848.3	c.647+153C>T		intron_variant		1	NM_001145306.2	ENSP00000397087	P1
CDK6	ENST00000265734.8	c.647+153C>T		intron_variant		1		ENSP00000265734	P1
CDK6	ENST00000473078.1	n.348C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26713 AN: 151972 Hom.: 3618 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0958

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0833

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.111 AC: 33720 AN: 303622 Hom.: 2434 Cov.: 4 AF XY: 0.112 AC XY: 17695 AN XY: 157710

Gnomad4 AFR exome AF: 0.367

Gnomad4 AMR exome AF: 0.0808

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.0852

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.176 AC: 26755 AN: 152090 Hom.: 3629 Cov.: 32 AF XY: 0.178 AC XY: 13226 AN XY: 74366

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.0957

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.0833

Gnomad4 OTH AF: 0.155

Alfa AF: 0.116 Hom.: 400

Bravo AF: 0.180

Asia WGS AF: 0.228 AC: 795 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.030
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs2301556; hg19: chr7-92300587;