rs1610912

Variant names:

• chr7-92615316-TATACA-T
• rs1610912
• NM_001145306.2:c.835-35_835-31delTGTAT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001145306.2(CDK6):​c.835-35_835-31delTGTAT 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
• Publications: 0 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 -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 rank	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.835-35_835-31delTGTAT		intron_variant	Intron 7 of 7	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.835-35_835-31delTGTAT		intron_variant	Intron 7 of 7		NP_001250.1
CDK6	XM_047419716.1	c.835-35_835-31delTGTAT		intron_variant	Intron 7 of 7		XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK6	ENST00000424848.3	c.835-35_835-31delTGTAT		intron_variant	Intron 7 of 7	1	NM_001145306.2	ENSP00000397087.3
CDK6	ENST00000265734.8	c.835-35_835-31delTGTAT		intron_variant	Intron 7 of 7	1		ENSP00000265734.4
CDK6	ENST00000467166.1	n.207-35_207-31delTGTAT		intron_variant	Intron 1 of 1	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

GnomAD2 exomes AF: 0.183 AC: 44981 AN: 245744 AF XY: 0.186

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 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

African (AFR) AF: 0.0628 AC: 1995 AN: 31744

American (AMR) AF: 0.130 AC: 5786 AN: 44458

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 7133 AN: 25504

East Asian (EAS) AF: 0.0157 AC: 619 AN: 39306

South Asian (SAS) AF: 0.114 AC: 9669 AN: 84508

European-Finnish (FIN) AF: 0.231 AC: 12312 AN: 53216

Middle Eastern (MID) AF: 0.196 AC: 982 AN: 5004

European-Non Finnish (NFE) AF: 0.240 AC: 247891 AN: 1031864

Other (OTH) AF: 0.213 AC: 12183 AN: 57324

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

African (AFR) AF: 0.0721 AC: 2994 AN: 41520

American (AMR) AF: 0.165 AC: 2523 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 986 AN: 3466

East Asian (EAS) AF: 0.0164 AC: 85 AN: 5188

South Asian (SAS) AF: 0.104 AC: 501 AN: 4820

European-Finnish (FIN) AF: 0.222 AC: 2346 AN: 10554

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17033 AN: 67922

Other (OTH) AF: 0.209 AC: 442 AN: 2110

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

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.86
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1610912; hg19: chr7-92244630;