12-55967092-G-A

Variant names:

• chr12-55967092-G-A
• rs2069398
• NM_001798.5:c.84G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001798.5(CDK2):​c.84G>A​(p.Glu28Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 1,613,304 control chromosomes in the GnomAD database, including 7,962 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 0.13 (2043 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5919 hom.)
• Consequence: CDK2 NM_001798.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.890
• Publications: 27 publications found

Genes affected

CDK2 (HGNC:1771): (cyclin dependent kinase 2) This gene encodes a member of a family of serine/threonine protein kinases that participate in cell cycle regulation. The encoded protein is the catalytic subunit of the cyclin-dependent protein kinase complex, which regulates progression through the cell cycle. Activity of this protein is especially critical during the G1 to S phase transition. This protein associates with and regulated by other subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A), and p27Kip1 (CDKN1B). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ENSG00000258554 (HGNC:):

PMEL (HGNC:10880): (premelanosome protein) This gene encodes a melanocyte-specific type I transmembrane glycoprotein. The encoded protein is enriched in melanosomes, which are the melanin-producing organelles in melanocytes, and plays an essential role in the structural organization of premelanosomes. This protein is involved in generating internal matrix fibers that define the transition from Stage I to Stage II melanosomes. This protein undergoes a complex pattern of prosttranslational processing and modification that is essential to the proper functioning of the protein. A secreted form of this protein that is released by proteolytic ectodomain shedding may be used as a melanoma-specific serum marker. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=0.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001798.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK2	NM_001798.5	MANE Select	c.84G>A	p.Glu28Glu	synonymous	Exon 1 of 7	NP_001789.2
	CDK2	NM_052827.4		c.84G>A	p.Glu28Glu	synonymous	Exon 1 of 6	NP_439892.2
	CDK2	NM_001290230.2		c.84G>A	p.Glu28Glu	synonymous	Exon 1 of 5	NP_001277159.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK2	ENST00000266970.9	TSL:1 MANE Select	c.84G>A	p.Glu28Glu	synonymous	Exon 1 of 7	ENSP00000266970.4
	CDK2	ENST00000354056.4	TSL:1	c.84G>A	p.Glu28Glu	synonymous	Exon 1 of 6	ENSP00000243067.4
	CDK2	ENST00000553376.5	TSL:5	c.84G>A	p.Glu28Glu	synonymous	Exon 1 of 8	ENSP00000452514.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19854 AN: 152170 Hom.: 2011 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0758

Gnomad ASJ AF: 0.0856

Gnomad EAS AF: 0.00635

Gnomad SAS AF: 0.0557

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.0796 AC: 19725 AN: 247936 AF XY: 0.0754

Gnomad AFR exome AF: 0.295

Gnomad AMR exome AF: 0.0575

Gnomad ASJ exome AF: 0.0809

Gnomad EAS exome AF: 0.00561

Gnomad FIN exome AF: 0.0722

Gnomad NFE exome AF: 0.0763

Gnomad OTH exome AF: 0.0743

GnomAD4 exome AF: 0.0816 AC: 119203 AN: 1461016 Hom.: 5919 Cov.: 31 AF XY: 0.0797 AC XY: 57944 AN XY: 726736

African (AFR) AF: 0.296 AC: 9910 AN: 33456

American (AMR) AF: 0.0621 AC: 2770 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.0802 AC: 2096 AN: 26122

East Asian (EAS) AF: 0.00446 AC: 177 AN: 39698

South Asian (SAS) AF: 0.0542 AC: 4673 AN: 86140

European-Finnish (FIN) AF: 0.0734 AC: 3916 AN: 53322

Middle Eastern (MID) AF: 0.0763 AC: 440 AN: 5768

European-Non Finnish (NFE) AF: 0.0809 AC: 89866 AN: 1111508

Other (OTH) AF: 0.0887 AC: 5355 AN: 60376

GnomAD4 genome AF: 0.131 AC: 19944 AN: 152288 Hom.: 2043 Cov.: 32 AF XY: 0.128 AC XY: 9541 AN XY: 74474

African (AFR) AF: 0.283 AC: 11768 AN: 41518

American (AMR) AF: 0.0757 AC: 1158 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0856 AC: 297 AN: 3470

East Asian (EAS) AF: 0.00636 AC: 33 AN: 5188

South Asian (SAS) AF: 0.0558 AC: 269 AN: 4824

European-Finnish (FIN) AF: 0.0689 AC: 732 AN: 10628

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0784 AC: 5336 AN: 68032

Other (OTH) AF: 0.108 AC: 229 AN: 2116

Alfa AF: 0.0976 Hom.: 827

Bravo AF: 0.138

Asia WGS AF: 0.0750 AC: 260 AN: 3478

EpiCase AF: 0.0774

EpiControl AF: 0.0767

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	15
DANN	Benign	0.95
PhyloP100		0.89
PromoterAI		-0.0084	Neutral
Mutation Taster		=99/1	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: rs2069398; hg19: chr12-56360876; COSMIC: COSV57186031; COSMIC: COSV57186031;