chr7-92615316-TATACA-T

Position:

• chr7-92615316-TATACA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001145306.2(CDK6):​c.835-35_835-31del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,525,002 control chromosomes in the GnomAD database, including 38,355 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2993 hom., cov: 27)
  • Exomes 𝑓: 0.22 (35362 hom.)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.862

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 -10 ACMG points.

• BP6: Variant 7-92615316-TATACA-T is Benign according to our data. Variant chr7-92615316-TATACA-T is described in ClinVar as [Benign]. Clinvar id is 1252462.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.835-35_835-31del		intron_variant		ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.835-35_835-31del		intron_variant			NP_001250.1
CDK6	XM_047419716.1	c.835-35_835-31del		intron_variant			XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK6	ENST00000424848.3	c.835-35_835-31del		intron_variant		1	NM_001145306.2	ENSP00000397087	P1
CDK6	ENST00000265734.8	c.835-35_835-31del		intron_variant		1		ENSP00000265734	P1
CDK6	ENST00000467166.1	n.207-35_207-31del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27294 AN: 151956 Hom.: 2999 Cov.: 27

Gnomad AFR AF: 0.0722

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.0163

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.211

GnomAD3 exomes AF: 0.183 AC: 44981 AN: 245744 Hom.: 4844 AF XY: 0.186 AC XY: 24761 AN XY: 133216

Gnomad AFR exome AF: 0.0681

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.0135

Gnomad SAS exome AF: 0.117

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.217 AC: 298570 AN: 1372928 Hom.: 35362 AF XY: 0.215 AC XY: 148047 AN XY: 688234

Gnomad4 AFR exome AF: 0.0628

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.280

Gnomad4 EAS exome AF: 0.0157

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.179 AC: 27285 AN: 152074 Hom.: 2993 Cov.: 27 AF XY: 0.177 AC XY: 13187 AN XY: 74354

Gnomad4 AFR AF: 0.0721

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.209

Alfa AF: 0.226 Hom.: 750

Bravo AF: 0.173

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1610912; hg19: chr7-92244630;